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Pavlou M, Serbis A, Kostara M, Challa A, Siomou E. Bone Metabolism Defects in Children With Idiopathic Hypercalciuria: An Update. Cureus 2025; 17:e82931. [PMID: 40416164 PMCID: PMC12103250 DOI: 10.7759/cureus.82931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2025] [Indexed: 05/27/2025] Open
Abstract
Idiopathic hypercalciuria (IH) in adults is considered to be the most common identifiable metabolic risk factor for calcium nephrolithiasis, also contributing to osteopenia and osteoporosis. Data on children and adolescents associating IH with bone metabolism show that up to one-third of such patients present with lower bone mineral density (BMD), increasing the risk of osteopenia, osteoporosis, and bone fractures in adulthood. Several factors, such as the degree of hypercalciuria and the presence of calcium urolithiasis, seem to affect the severity of bone metabolism abnormalities in children with IH. In order to follow these patients, BMD has traditionally been estimated by dual-energy X-ray absorptiometry (DXA) scan. In children, chronological age should be taken into account when measuring BMD, as well as weight, height, and BMI. In addition, biochemical bone turnover markers provide surrogate indices of bone turnover and complement the static measurements of BMD. They respond rapidly to changes in bone physiology, and their measurement can be repeated more frequently. However, since children's bone mass increases constantly until after puberty, age, sex, and pubertal stage have to be taken into consideration when assessing these markers. In addition, relevant studies in children and adolescents have shown conflicting results. Regarding the management of patients with IH, identification and appropriate treatment are of great importance in order to prevent the formation of kidney stones, as well as to improve bone metabolism defects and decrease fracture risk. Such treatment measures include dietary interventions, potassium citrate supplementation and/or thiazide diuretics, and bisphosphonates in resistant cases. This review summarizes the latest data on bone metabolism defects in children and adolescents with IH, the possible pathomechanisms involved, the biochemical markers that could be used together with DXA to follow these patients, and the available treatment options.
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Affiliation(s)
- Maria Pavlou
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Anastasios Serbis
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Maria Kostara
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Anna Challa
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Ekaterini Siomou
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
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Heilberg IP, Carvalho AB, Denburg MR. Between a Rock and a Short Place-The Impact of Nephrolithiasis on Skeletal Growth and Development Across the Lifespan. Curr Osteoporos Rep 2024; 22:576-589. [PMID: 39356465 DOI: 10.1007/s11914-024-00888-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/10/2024] [Indexed: 10/03/2024]
Abstract
PURPOSE OF REVIEW The impact of nephrolithiasis on skeletal growth and bone health across the life span of kidney stone formers is reviewed. MAIN FINDINGS Bone disease is an early event among kidney stone formers (SF), with distinct phenotypes according to each age, sex, menopausal status, dietary, hormonal and genetic factors. Nephrolithiasis-associated bone disorder is characterized by reduced bone mineral density (BMD) and histologically discloses low bone formation, high bone resorption and abnormal mineralization. Although hypercalciuria has been presumed to be pathogenic for bone loss in SF, the association of BMD with urinary calcium is not uniform in all studies. Hypocitraturia, metabolic disturbances, cytokines and receptors, growth factors and acid-base status may all influence skeletal outcomes. The potential link of bone disease with vascular calcification and cardiovascular disease among SF is discussed. The unique vulnerability of the younger skeleton to the effects of nephrolithiasis on attainment of peak bone mass and strength is highlighted and the association of bone loss with kidney stone formation early in life indicate the opportunity for intervention to reduce the risk of future bone fractures.
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Affiliation(s)
- Ita Pfeferman Heilberg
- Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Botucatu 740 - Vila Clementino, São Paulo, 04023-900, Brazil.
| | - Aluizio Barbosa Carvalho
- Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Botucatu 740 - Vila Clementino, São Paulo, 04023-900, Brazil
| | - Michelle R Denburg
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
- Division of Pediatric Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
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Penido MGMG, Tavares MDS. Beyond kidney stones: Why pediatricians should worry about hypercalciuria. World J Clin Pediatr 2021; 10:137-150. [PMID: 34868890 PMCID: PMC8603641 DOI: 10.5409/wjcp.v10.i6.137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/08/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of urolithiasis (UL) is increasing, and it has become more common in children and adolescents over the past few decades. Hypercalciuria is the leading metabolic risk factor of pediatric UL, and it has high morbidity, with or without lithiasis as hematuria and impairment of bone mass. The reduction in bone mineral density has already been described in pediatric idiopathic hypercalciuria (IH), and the precise mechanisms of bone loss or failure to achieve adequate bone mass gain remain unknown. A current understanding is that hypercalciuria throughout life can be considered a risk of change in bone structure and low bone mass throughout life. However, it is still not entirely known whether hypercalciuria throughout life can compromise the quality of the mass. The peak bone mass is achieved by late adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference in order to achieve the peak of optimal bone mass. The bone mass acquired during childhood and adolescence is a major determinant of adult bone health, and its accumulation should occur without interference. This raises the critical question of whether adult osteoporosis and the risk of fractures are initiated during childhood. Pediatricians should be aware of this pediatric problem and investigate their patients. They should have the knowledge and ability to diagnose and initially manage patients with IH, with or without UL.
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Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Pediatric Nephrology Unit, Nephrology Center, Santa Casa de Belo Horizonte Hospital, CEP 30150320, Belo Horizonte, Minas Gerais, Brazil
- Pediatric Nephrology Unit, Pediatric Department, Clinics Hospital, Universidade Federal de Minas Gerais, CEP 30130100, Belo Horizonte, Minas Gerais, Brazil
| | - Marcelo de Sousa Tavares
- Pediatric Nephrology Unit, Nephrology Center, Santa Casa de Belo Horizonte Hospital, CEP 30150320, Belo Horizonte, Minas Gerais, Brazil
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Penido MGMG, Tavares MDS. Should pediatric idiopathic hypercalciuria be treated with hypocalciuric agents? World J Nephrol 2021; 10:47-58. [PMID: 34430384 PMCID: PMC8353600 DOI: 10.5527/wjn.v10.i4.47] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 07/18/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hypercalciuria is the most common metabolic risk factor for calcium urolithiasis and is associated with bone loss in adult patients. Reduced bone mineral density (BMD) was already described in idiopathic hypercalciuria (IH) children, but the precise mechanisms of bone loss or inadequate bone mass gain remain unknown. Life-long hypercalciuria might be considered a risk to change bone structure and determine low bone mass throughout life. The peak of bone mass should occur without interferences. A beneficial effect of citrate formulations and thiazides on bone mass in adult and pediatric patients with IH have been shown.
AIM To evaluate whether pharmacological therapy has a beneficial effect on bone mass in children and adolescents with IH.
METHODS This retrospective cohort study evaluated 40 hypercalciuric children non-responsive to lifestyle and diet changes. After a 2-mo run-in period of citrate formulation (Kcitrate) usage, the first bone densitometry (DXA) was ordered. In patients with sustained hypercalciuria, a thiazide diuretic was prescribed. The second DXA was performed after 12 mo. Bone densitometry was performed by DXA at lumbar spine (L2-L4). A 24-h urine (calcium, citrate, creatinine) and blood samples (urea, creatinine, uric acid, calcium, phosphorus, magnesium, chloride, hemoglobin) were obtained. Clinical data included age, gender, weight, height and body mass index.
RESULTS Forty IH children; median age 10.5 year and median time follow-up 6.0 year were evaluated. Nine patients were treated with Kcitrate (G1) and 31 with Kcitrate + thiazide (G2). There were no differences in age, gender, body mass index z-score and biochemical parameters between G1 and G2. There were no increases in total cholesterol, kalemia and magnesemia. Calciuria decreased in both groups after treatment. Lumbar spine BMD z-score increased after thiazide treatment in G2. There was no improvement in G1.
CONCLUSION Results point to a beneficial effect of thiazide on lumbar spine BMD z-score in children with IH. Further studies are necessary to confirm the results of the present study.
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Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Pediatric Nephrology Unit, Nephrology Center of Santa Casa de Belo Horizonte, Belo Horizonte 30150320, Minas Gerais, Brazil
- Federal University of Minas Gerais, Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology Unit, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Marcelo de Sousa Tavares
- Pediatric Nephrology Unit, Nephrology Center of Santa Casa de Belo Horizonte, Belo Horizonte 30150320, Minas Gerais, Brazil
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Perez-Suarez G, Yanes MIL, de Basoa MCMF, Almeida ES, García Nieto VM. Evolution of bone mineral density in patients with idiopathic hypercalciuria: a 20-year longitudinal study. Pediatr Nephrol 2021; 36:661-667. [PMID: 32980941 DOI: 10.1007/s00467-020-04754-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 07/06/2020] [Accepted: 09/01/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Several recent studies reported bone mineral density (BMD) reduction in pediatric patients with idiopathic hypercalciuria (IH). This longitudinal study aimed to evaluate BMD evolution in IH patients through three bone densitometry studies conducted over 20 years on average. A second objective was to evaluate urine calcium and citrate excretion during this period. METHODS Case notes of 34 patients diagnosed with IH at age 7.9 ± 3, alongside results of two bone densitometry studies, performed at 10.5 ± 2.7 (BMD1) and 14.5 ± 2.7 (BMD2) years of age, were reviewed. Patients underwent a third densitometry study in adulthood (BMD3) aged 28.3 ± 2.9. Mean follow-up duration (time-lapse between BMD1 and BMD3) was 17.7 ± 1.4 years. RESULTS Statistically significant differences were found between z-BMD3 (- 0.85 ± 1.10) and z-BMD1 (- 1.47 ± 0.99) (P = 0.001) as well as between z-BMD3 and z-BMD2 (- 1.33 ± 1.20) (P = 0.016). At the end of follow-up, z-BMD3 was superior to z-BMD2 in 23 adult patients (67.6%) and lower in 11 patients (5M, 6F; 32.3%). Both men and women showed increased bone mass over time, although such increases were significant only for women. The gradual decrease observed in calcium/creatinine and citrate/creatinine ratios could be related to improvement in osteoblastic activity and especially reduction in osteoclastic activity. CONCLUSIONS In patients with IH, BMD improves, which may be related especially to female sex, increment of body mass, and reduction in bone resorption. Upon reaching adulthood, urine calcium and citrate excretion tend to decrease so lithogenic risk still remains. The cause of the latter is unknown, although it likely relates to changes in bone activity.
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Affiliation(s)
- German Perez-Suarez
- Nephrology Department, Hospital Universitario Insular de Las Palmas de Gran Canaria, Las Palmas, Canary Islands, Spain.
| | - Ma Isabel Luis Yanes
- Pediatric Nephrology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain
| | | | | | - Víctor M García Nieto
- Pediatric Nephrology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain
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Lu YM, Li CC, Juan YS, Lee YC, Chien TM. Urolithiasis increases the risk of subsequent onset of osteoporosis. J Bone Miner Metab 2020; 38:38-43. [PMID: 31290006 DOI: 10.1007/s00774-019-01022-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 06/11/2019] [Indexed: 11/28/2022]
Abstract
Urolithiasis and osteoporosis are two different pathological entities, but are both important public health issues in older patients. Moreover, the two diseases may share some similar pathogenesis pathway. Currently, few studies focus on the relationship between urolithiasis and osteoporosis. Furthermore, whether the common mobilities influence the long-term osteoporosis rate in urolithiasis patients has never been studied. In the present study, we used the Taiwan National Health Insurance Database (LHID 2000) compiled by the NHI from 1996 to 2013 to determine whether urolithiasis influenced long-term osteoporosis; controls were matched for age, sex, and other comorbidities (including hypertension, diabetes mellitus, dyslipidemia, liver disease, and cardiovascular disease). We included a total of 91,254 patients, including 22,575 patients with urolithiasis and 68,679 control patients. There was a significant difference between the incidence of osteoporosis between the urolithiasis and control groups (adjusted hazard ratio 1.34, 95% CI 1.19-1.79, p < 0.001) during the follow up. The incidence rate of osteoporosis during the follow-up period was 8.87 per 1000 person-years in the urolithiasis group and 6.37 per 1000 person-years in the control group. Based on our results, it is evident that urolithiasis significantly increases the subsequent osteoporosis rate. Though the clinical mechanisms are not fully understood, patients who have a history of urolithiasis may need regular follow-up assessment of bone marrow density.
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Affiliation(s)
- Yen-Man Lu
- Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
- Department of Urology, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, Kaohsiung, 807, Taiwan
| | - Ching-Chia Li
- Department of Urology, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, Kaohsiung, 807, Taiwan
- Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yung-Shun Juan
- Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Yung-Chin Lee
- Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Tsu-Ming Chien
- Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
- Department of Urology, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, Kaohsiung, 807, Taiwan.
- Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Does idiopathic hypercalciuria affect bone metabolism during childhood? A prospective case-control study. Pediatr Nephrol 2018; 33:2321-2328. [PMID: 30043116 DOI: 10.1007/s00467-018-4027-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 07/06/2018] [Accepted: 07/17/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND A limited number of studies have evaluated biochemical bone metabolism markers in children with idiopathic hypercalciuria, which in adults has been linked with osteopenia. Our aim was to investigate in children with idiopathic hypercalciuria biochemical markers of bone formation and resorption and the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kB ligand (sRANKL) system which is involved in the osteoclastogenesis process. METHODS A prospective study was conducted on 50 children with idiopathic hypercalciuria and 50 healthy age-, sex-, and Tanner stage-matched control subjects. Following the diagnosis, patients were requested to follow a 3-month dietary recommendation for idiopathic hypercalciuria. In patients, at diagnosis and at 3 months of follow-up, and in controls, bone-related hormones and serum/urine biochemical parameters were studied. The bone formation markers (total ALP and osteocalcin) and the bone resorption markers (β-Crosslaps) and the OPG and sRANKL levels were determined. RESULTS No differences were found in the bone formation markers or OPG and sRANKL between the children with idiopathic hypercalciuria and controls. The β-Crosslaps and the β-Crosslaps/osteocalcin ratio were higher in the patients at diagnosis than in controls (p = 0.019 and p = 0.029, respectively), with a trend to decrease after the 3-month dietary intervention. The initially increased 24-h urinary Ca in the patients decreased after the 3-month dietary intervention (p = 0.002). CONCLUSIONS Children with idiopathic hypercalciuria had biochemical markers compatible with normal bone formation but increased bone resorption. After a 3-month dietary intervention, the trend observed towards decrease in the serum β-Crosslaps may reflect a beneficial response.
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Role of FGF23 in Pediatric Hypercalciuria. BIOMED RESEARCH INTERNATIONAL 2018; 2017:3781525. [PMID: 29457024 PMCID: PMC5804327 DOI: 10.1155/2017/3781525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/26/2017] [Accepted: 10/22/2017] [Indexed: 01/29/2023]
Abstract
Background This study explored the possible role of FGF23 in pediatric hypercalciuria. Methods Plasma FGF23 was measured in 29 controls and 58 children and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34 after 6 months of treatment (Treated). Hypercalciuric patients also measured serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine calcium, phosphate, and creatinine. Results There were no differences in age, gender, ethnicity, or body mass index either between controls and patients, or between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72 compared with all patients, 58 RU/mL (p = 0.0019). However, whereas FGF23 in Pre-Treated patients, 73 RU/mL, was not different from controls, in Treated patients it was 50 RU/mL, significantly lower than in both controls (p < 0.0001) and Pre-Treated patients (p = 0.02). In all patients, there was a correlation between FGF23 and urinary calcium (r = 0.325; p = 0.0014). Treated patients had significantly lower urinary calcium (p < 0.0001), higher TP/GFR (p < 0.001), and higher serum phosphate (p = 0.007) versus Pre-Treated patients. Conclusions Pharmacological treatment of hypercalciuric patients resulted in significantly lower urinary calcium excretion, lower serum FGF23, and elevated TP/GFR and serum phosphate concentration, without significant changes in PTH. Further studies are indicated. This trial is registered with Clinical Registration Number RBR 8W27X5.
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The value of hypercalciuria in patients with osteopenia versus osteoporosis. Urolithiasis 2016; 45:279-283. [PMID: 27480097 DOI: 10.1007/s00240-016-0909-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 07/25/2016] [Indexed: 10/21/2022]
Abstract
The aim of this study was to analyze the presence of lithogenic metabolic factors in the blood and urine of patients with osteopenia versus osteoporosis. This is a cross-sectional study including 67 patients who were divided into two groups according to the presence of either osteopenia or osteoporosis as measured by bone densitometry: group 1-40 patients with osteopenia (22 men and 18 women) and group 2-27 patients with osteoporosis (13 men and 14 women). Metabolic studies were performed on the blood and urine; statistical analysis was performed comparing means and conducting linear correlation and multivariate analyses with SPSS. Statistical significance was considered to be p ≤ 0.05. The mean age of patients in group 1 was 52.9 ± 12.8 years versus 50.3 ± 11.4 in group 2; the difference was not statistically significant. In group 2, higher levels of osteocalcin, β-crosslaps, urinary calcium, fasting urine calcium/creatinine, 24 h urine calcium/creatinine and 24 h oxaluria were observed compared to group 1. In the multivariate analysis, only the β-crosslaps and urinary calcium were independently associated with osteoporosis. It would be advisable to determine the urinary calcium levels in patients with osteoporosis since altered levels may necessitate modifying the diagnostic and therapeutic approach to osteoporosis.
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Denburg MR, Leonard MB, Haynes K, Tuchman S, Tasian G, Shults J, Copelovitch L. Risk of fracture in urolithiasis: a population-based cohort study using the health improvement network. Clin J Am Soc Nephrol 2014; 9:2133-40. [PMID: 25341724 DOI: 10.2215/cjn.04340514] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Studies have shown decreased bone mineral density in individuals with urolithiasis, but their burden of fracture remains unclear. This study sought to determine whether urolithiasis is associated with increased fracture risk across the lifespan and to delineate sex effects. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A population-based retrospective cohort study using The Health Improvement Network was performed. The median calendar year for the start of the observation period was 2004 (1994-2012). This study identified 51,785 participants with ≥1 of 87 diagnostic codes for urolithiasis and 517,267 randomly selected age-, sex-, and practice-matched participants. Cox regression was used to estimate the hazard ratio (HR) for first fracture. Fractures identified using diagnostic codes were classified by anatomic site. RESULTS Median age was 53 years, and 67% of participants were men, confirming their greater urolithiasis burden. Median time from urolithiasis diagnosis to fracture was 10 years. The HR for fracture associated with urolithiasis differed by sex and age (P for interactions, P≤0.003). In men, the adjusted HR was greatest in adolescence (1.55; 95% confidence interval [95% CI], 1.07 to 2.25) with an overall HR of 1.10 (95% CI, 1.05 to 1.16). Urolithiasis was associated with higher fracture risk in women aged 30-79 years (HR, 1.17-1.52), and was highest in women aged 30-39 years (HR, 1.52; 95% CI, 1.23 to 1.87). Peak background fracture rates were highest in boys aged 10-19 years and in women aged 70-79 years. The incidence per 10,000 person-years in participants with versus without urolithiasis was 392 versus 258 in male participants aged 10-19 years, and 263 versus 218 in women aged 70-79 years. Distribution of fracture site within sex did not differ between participants with versus without urolithiasis. CONCLUSIONS Urolithiasis was associated with higher incident fracture risk. The significantly higher risk at times of peak background fracture incidence in adolescent boys and elderly women has profound public health implications.
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Affiliation(s)
- Michelle R Denburg
- Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
| | - Mary B Leonard
- Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kevin Haynes
- Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania; and
| | - Shamir Tuchman
- George Washington University School of Medicine, Children's National Medical Center, Washington, DC
| | - Gregory Tasian
- Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Justine Shults
- Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Lawrence Copelovitch
- Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Abstract
PURPOSE OF REVIEW To review the recent publications describing the link between pediatric nephrolithiasis and bone metabolism. RECENT FINDINGS Nephrolithiasis incidence is increasing in children and is associated with low bone mineral density (BMD). Affected children are conceptually at risk for fractures and osteoporosis. In addition to abnormal calcium metabolism, inflammation, genetic makeup and dietary habits are being recognized as important factors in the pathophysiology of nephrolithiasis and low bone density. Findings from retrospective reviews suggest that low BMD in children may be improved with citrate or thiazide treatment. SUMMARY The healthcare burden from low BMD with subsequent osteoporosis and fracture risk is immense with potential far-reaching effects in patient quality of life and healthcare expense. Bone mass is acquired in the pediatric age range, thus it is important to identify and treat at-risk children. Retrospective reviews in pediatric patients indicate that citrate or thiazide diuretic treatment may improve BMD. We now understand that a relationship exists between nephrolithiasis and low BMD. To improve healthcare for our current patients as well as protect their future health it is important to identify low BMD and initiate strategies to improve BMD in 'at-risk' children.
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Akın Y, Uçar M, Yücel S. Current medical treatment in pediatric urolithiasis. Turk J Urol 2013; 39:253-63. [PMID: 26328120 DOI: 10.5152/tud.2013.063] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Accepted: 04/30/2013] [Indexed: 11/22/2022]
Abstract
Although the prevalence of urolithiasis is nearly 2-3% in childhood, the risk of recurrence may range from 6.5-54%. There has been an increase in urinary stone disease among pediatric age groups, and stone disease has a multifactorial etiology. After the diagnosis, detailed metabolic evaluation is required. High recurrence rates, therapeutic irregularities and deficiency in diagnosis may lead to comorbidities such as loss of kidney function. Following diagnosis, the requirement for surgery, such as stone extraction and correction of anatomical anomalies, is determined. Medical and supportive treatments are also needed to prevent recurrence and urinary tract infections and to preserve renal function. Supportive care includes increased fluid intake and dietary modifications. Medical treatment is dependent on the cause of the urinary stone disease. The morbidities associated with pediatric urolithiasis can be prevented by early diagnosis, detailed metabolic analysis, regular follow-up and medical treatment protocols.
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Affiliation(s)
- Yiğit Akın
- Department of Urology, Faculty of Medicine, Erzincan University, Erzincan, Turkey
| | - Murat Uçar
- Department of Urology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Selçuk Yücel
- Department of Urology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
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Arrabal-Polo MÁ, Sierra Girón-Prieto M, Orgaz-Molina J, Zuluaga-Gómez A, Arias-Santiago S, Arrabal-Martín M. Calcium renal lithiasis and bone mineral density. Importance of bone metabolism in urinary lithiasis. Actas Urol Esp 2013; 37:362-7. [PMID: 23411066 DOI: 10.1016/j.acuro.2012.10.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2012] [Accepted: 10/25/2012] [Indexed: 12/14/2022]
Abstract
CONTEXT Calcium Nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphor-calcium metabolism. OBJECTIVE To establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites. EVIDENCE ACQUISITION We performed a PubMed literature review using different MeSH Terms like "Nephrolithiasis", "Bone mineral density", "Urinary stones", "Calcium", Bone resorption" and "Bone formation", with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected. EVIDENCE SYNTHESIS In different studies reviewed have been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and β-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients. CONCLUSION We recommend perform markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III.
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Affiliation(s)
- M Á Arrabal-Polo
- Servicio de Urología, Hospital Universitario San Cecilio, Granada, España.
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Arrabal-Polo MA, Arias-Santiago S, de Haro-Muñoz T, Lopez-Ruiz A, Orgaz-Molina J, Gonzalez-Torres S, Zuluaga-Gomez A, Arrabal-Martin M. Effects of Aminobisphosphonates and Thiazides in Patients With Osteopenia/Osteoporosis, Hypercalciuria, and Recurring Renal Calcium Lithiasis. Urology 2013; 81:731-7. [DOI: 10.1016/j.urology.2012.12.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Revised: 11/05/2012] [Accepted: 12/09/2012] [Indexed: 11/25/2022]
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Nacaroglu HT, Demircin G, Bülbül M, Erdogan O, Akyüz SG, Caltik A. The association between urinary tract infection and idiopathic hypercalciuria in children. Ren Fail 2013; 35:327-32. [PMID: 23394064 DOI: 10.3109/0886022x.2013.764254] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Identifying the risk factors is important in prevention of urinary tract infections (UTIs) in children. The aim of this study is to evaluate the association of UTI and idiopathic hypercalciuria (IHC). METHODS Two hundred and twenty-four children aged between 1 month and 16 years and diagnosed to have UTI were evaluated for urinary calcium excretion. The children were diagnosed to have IHC if their urinary calcium/creatinine ratios in at least two different spot urine samples were >0.6 between 0-1 year old and ≥0.21 over 1 year or daily calcium excretion >4 mg/kg. RESULTS The frequency of IHC was found to be 16.7%. Family history of urolithiasis, parental consanguinity, presentation with abdominal pain, loss of appetite, and discomfort were found to be significantly higher in the IHC group. No association was found between IHC and the recurrence of UTI, presence of vesicoureteral reflux, renal scar formation, and the prognosis. CONCLUSIONS IHC should be considered among the risk factors for UTI and should be investigated particularly in patients with family history of urinary stones and suggestive complaints of IHC.
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Osteopenia/osteoporosis in patients with calcium nephrolithiasis. ACTA ACUST UNITED AC 2012; 40:709-16. [PMID: 22886308 DOI: 10.1007/s00240-012-0497-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Accepted: 08/02/2012] [Indexed: 01/06/2023]
Abstract
The objective of this study is to analyze the alterations in bone mineral density and bone and calcium-phosphorus metabolism in patients with calcium nephrolithiasis. We designed a study with 182 patients who were distributed among three groups: group O, 56 patients without nephrolithiasis; group A, 67 patients with calcium nephrolithiasis and mild lithogenic activity; and group B, 59 patients with calcium nephrolithiasis and severe lithogenic activity. Metabolic parameters of blood and urine that were related to calcium-phosphorous and bone metabolism and bone densitometry were assessed in all patients. A comparative study was performed on the variables of bone and calcium-phosphorus metabolism and bone densitometry as well as the presence or absence of osteopenia/osteoporosis. The patients in group B had a greater loss of bone mineral density, measured by the T-score, than the patients in groups O and A. Moreover, the proportion of patients in group B with osteopenia/osteoporosis was statistically significantly higher than the proportion of patients in groups O and A. We observed higher values of calciuria, fasting calcium/creatinine ratio, and 24-h calcium/creatinine among the patients in group B compared to the other two groups. Calciuria, citraturia, and fasting calcium/creatinine were independent factors that showed a relationship with severe lithogenic activity compared to the control group, and β-crosslaps is an independent factor that has a relationship with severe lithogenic activity as compared to mild lithogenic activity. Patients with calcium lithiasis and severe lithogenic activity have a greater loss in bone mineral density and therefore a greater risk of osteopenia/osteoporosis.
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Mäyränpää MK, Viljakainen HT, Toiviainen-Salo S, Kallio PE, Mäkitie O. Impaired bone health and asymptomatic vertebral compressions in fracture-prone children: a case-control study. J Bone Miner Res 2012; 27:1413-24. [PMID: 22367922 DOI: 10.1002/jbmr.1579] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Frequent fractures in children may be a sign of impaired bone health, but it remains unestablished when and how fracture-prone children should be assessed. This prospective study elucidated skeletal characteristics and predisposing factors in children with recurrent fractures. Findings were used to establish guidelines for screening. During a 12-month period we recorded fracture history for all children (n = 1412) treated for an acute fracture at a large university hospital. All apparently healthy children over 4 years of age, who had sustained: (1) at least one vertebral fracture; (2) two long-bone fractures before age 10 years; or (3) three long-bone fractures before age 16 years, were recruited. They underwent dual-energy X-ray absorptiometry (DXA), laboratory tests, and spinal radiography. Information regarding family history and lifestyle factors were collected. Findings were compared with healthy controls. Sixty-six fracture-prone children (44 males, mean age 10.7 years; 5% of all children with fractures) were identified. Altogether, they had sustained 183 long-bone fractures (median 3, range 0–7); 11 children had sustained vertebral fracture(s). Patients had significantly lower bone mineral density (BMD) at lumbar spine (p < 0.001), hip (p = 0.007), and whole body (p < 0.001) than the controls; only 5 children (8%) had a BMD Z-score < −2.0. Asymptomatic vertebral compressions were prevalent, especially in those under 10 years of age. Hypercalciuria (11%) and hyperphosphaturia (22%) were significantly more prevalent than in controls. Serum concentration of 25-hydroxyvitamin D (S-25OHD) was below 50 nmol/L in 55%; low levels were associated with low BMD and vertebral compressions. The fracture-prone children had lower calcium intake, less physical activity, and more often had siblings with fractures than the controls. The findings suggest that a thorough pediatric evaluation, including DXA and spinal radiography, is often indicated already after a second significant low-energy fracture in children, in order to detect potentially preventable adverse lifestyle factors and nutritional deficits and to identify those with compromised overall bone health.
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Affiliation(s)
- Mervi K Mäyränpää
- Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Stenbäckinkatu 11, HUS, Helsinki, Finland.
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Plasma and urinary levels of cytokines in patients with idiopathic hypercalciuria. Pediatr Nephrol 2012; 27:941-8. [PMID: 22223141 DOI: 10.1007/s00467-011-2094-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2011] [Revised: 12/02/2011] [Accepted: 12/05/2011] [Indexed: 10/14/2022]
Abstract
BACKGROUND Recent studies suggest that cytokines modulate bone turnover. Idiopathic hypercalciuria (IH) seems to be associated with bone mineral loss. Therefore, the aim of this study was to assess cytokines involved in bone turnover in patients with IH. METHODS Plasma and spot-urine levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein (MCP-1) were measured in 70 children and adolescents with IH and in 37 healthy controls. Patients with IH were subdivided according to their calciuria at the time of sample collection: ≥4 mg/kg/day (persistent IH, n=27) and below 4 mg/kg/day (controlled IH, n=43). Cytokines were determined by enzyme-linked immunoassay. RESULTS Plasma and urinary concentrations of IL-1β, IL-6, IL-8, and TNF-α were undetectable in all groups. No differences were found between controlled and persistent hypercalciuria for plasma and urinary levels of MCP-1 and TGF-β1. On the other hand, MCP-1 levels were significantly higher in both subgroups of IH in comparison to healthy controls. Furthermore, urinary MCP-1 levels of IH patients correlated positively with bone mineral content (p=0.013). CONCLUSION Although cytokine measurements did not allow the differentiation between persistent and controlled IH, our findings suggest that MCP-1 might play a role in patients with IH.
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Moreira Guimarães Penido MG, de Sousa Tavares M. Bone disease in pediatric idiopathic hypercalciuria. World J Nephrol 2012; 1:54-62. [PMID: 24175242 PMCID: PMC3782196 DOI: 10.5527/wjn.v1.i2.54] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2011] [Revised: 11/11/2011] [Accepted: 02/10/2012] [Indexed: 02/06/2023] Open
Abstract
Idiopathic hypercalciuria (IH) is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density (BMD), as described previously in pediatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs (gut, bone and kidney), which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins (i.e., fibroblast growth-factor-23). Usually, a primary defect in one organ induces compensatory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary to a primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular transport of this ion in intestines, kidneys and bones. Reduced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.
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Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Maria Goretti Moreira Guimarães Penido, Marcelo de Sousa Tavares, Department of Pediatrics, Pediatric Nephrology Unit, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Belo Horizonte, CEP 30130100, Minas Gerais, Brazil
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Effect of thiazides on bone mineral density in children with idiopathic hypercalciuria. Pediatr Nephrol 2012; 27:261-8. [PMID: 21874585 DOI: 10.1007/s00467-011-1987-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2010] [Revised: 07/20/2011] [Accepted: 08/01/2011] [Indexed: 02/07/2023]
Abstract
To determine the effect of thiazide treatment on bone mineral density (BMD) in children with idiopathic hypercalciuria (IH) and osteopenia, we reviewed the case notes of 22 children aged 11.7 ± 2.7 years diagnosed with IH and osteopenia who had received thiazides for 2.4 years. The data on this group were compared with those of 32 IH children with osteopenia aged 11.2 ± 2.7 years who had not received thiazide treatment. By the end of the follow-up period, the z-BMD had improved spontaneously in 23 of the 32 control children (72%) and in 12 of the 22 patients on thiazides (54%). Although treated patients had a higher body mass index (BMI) and a higher BMD following treatment, the differences became statistically negligible when these parameters were expressed as z-BMD or as bone mineral apparent density (BMAD). In contrast, within the control group, there were significant differences in BMAD and z-BMD at the end of the follow-up. Patients who had an improved z-BMD at the end of the treatment also showed an increase in their BMI. Based on these results, we conclude that thiazide treatment does not improve the z-BMD in children with IH. More than half of the children suffering from IH enrolled in our study showed a spontaneous improvement in their z-BMD, which was more evident when the initial BMAD was not low and when their BMI increased during the follow-up period.
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Longitudinal study of bone mineral density in children with idiopathic hypercalciuria. Pediatr Nephrol 2012; 27:123-30. [PMID: 21779854 DOI: 10.1007/s00467-011-1952-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Revised: 06/08/2011] [Accepted: 06/10/2011] [Indexed: 12/18/2022]
Abstract
Children with idiopathic hypercalciuria (IH) may have a reduced bone mineral density (BMD), which could impact on bone health in adulthood. There is currently no strong evidence for a preferred treatment of such children. The aim of our study was to evaluate the BMD z-score before and after treating children and adolescents with IH with potassium citrate and thiazides. The study consisted of a historical cohort of 80 pediatric patients who were evaluated between October 1989 and November 2010. Bone scanning and densitometry measurements were made with dual-emission X-ray absorptiometry. Lumbar-spine BMD (g/cm(2)) and BMD z-score were evaluated before and after treatment. The t test and Mann-Whitney U test were used for statistical analysis. Forty-three boys and 37 girls were followed for a median time of 6.0 years. Median calcium excretion before and after treatment was 5.0 and 2.6 mg/kg/24 h, respectively. The BMD z-score changed significantly from -0.763 ± 0.954 (mean ± SD) to -0.537 ± 0.898 (p < 0.0001) before and after treatment, respectively. The BMD z-score of the patients improved with treatment, suggesting a beneficial effect and potential need for treatment. However, the lack of a control group points to the need for future studies to corroborate this outcome.
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Arrabal-Polo MA, Arrabal-Martin M, de Haro-Munoz T, Lopez-Leon VM, Merino-Salas S, Ochoa-Hortal MA, Garrido-Gomez J, Lahoz-Garcia C, Zuluaga-Gomez A. Mineral density and bone remodelling markers in patients with calcium lithiasis. BJU Int 2011; 108:1903-1908. [DOI: 10.1111/j.1464-410x.2011.10167.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Arrabal-Polo MA, Arrabal-Martin M, de Haro-Muñoz T, Poyatos-Andujar A, Palæo-Yago F, Zuluaga-Gomez A. Biochemical determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis. Urology 2011; 79:48-54. [PMID: 21908029 DOI: 10.1016/j.urology.2011.07.1382] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2011] [Revised: 06/04/2011] [Accepted: 07/09/2011] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To analyze the biochemical alterations in plasma and the urine determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis. METHODS We performed a cross-sectional study of 120 patients divided into 2 groups: group 1, 60 patients without nephrolithiasis; and group 2, 60 patients with severe and/or recurrent calcium nephrolithiasis. In all patients, a study of renal function, calcium metabolism, and bone remodeling markers, and a study of the lithogenic factors were performed in urine after fasting and in 24-hour urine samples. RESULTS We observed greater values for phosphorus in group 1 than in group 2 (P=.03). Also, we found greater values for intact parathyroid hormone (P=.01), osteocalcin (P=.000), and β-crosslaps (P=.000) in group 2 than in group 1. In the 24-hour urine samples, significant differences were found between groups 1 and 2 in calciuria (11.7 vs 17.4 mg/dL; P=.000), citraturia (50.6 vs 33.5 mg/dL; P=.002), calcium/creatinine quotient (0.14 vs 0.20; P=.001), calcium/citrate quotient (0.05 vs 0.13; P=.04), and calcium/creatinine quotient after fasting (0.09 vs 0.16; P=.000). CONCLUSION We consider the determinants of severe and/or recurrent calcium lithiasis to be hypercalciuria and hypocitraturia and a calcium/citrate quotient>0.06. As risk markers we can consider phosphatemia<2.9 mg/dL, phosphate/chlorine quotient>35, alkaline phosphatase>80 U/L, intact parathyroid hormone>60 pg/mL, osteocalcin>16 ng/mL, β-crosslaps>0.400 ng/mL, and β-crosslaps/osteocalcin quotient>0.028.
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Ranta S, Viljakainen H, Mäkipernaa A, Mäkitie O. Hypercalciuria in children with haemophilia suggests primary skeletal pathology. Br J Haematol 2011; 153:364-71. [DOI: 10.1111/j.1365-2141.2011.08639.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Santos ACS, Lima EM, Oliveira EA, Simões e Silva AC. Bone disease and cytokines in idiopathic hypercalciuria: a review. J Pediatr Endocrinol Metab 2011; 24:405-10. [PMID: 21932573 DOI: 10.1515/jpem.2011.243] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Bone remodeling is a continuous and dynamic process of skeletal destruction and renewal. A complex regulatory mechanism with the participation of several cytokines precisely defines the role of osteoclasts in the chain of events leading to bone resorption. There are multiple mechanisms underlying the regulation of bone resorption, which can involve increased calcium excretion and decreased bone density in patients with idiopathic hypercalciuria (IH). However, the pathogenesis of bone mass reduction in IH remains uncertain. The purpose of this review is to summarize the recent published evidence on the possible mechanisms by which cytokines could be associated with the pathogenesis of IH.
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Affiliation(s)
- Augusto C S Santos
- Department of Pediatrics, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil
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Zerwekh JE. Bone disease and hypercalciuria in children. Pediatr Nephrol 2010; 25:395-401. [PMID: 19885683 DOI: 10.1007/s00467-009-1338-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2009] [Revised: 10/05/2009] [Accepted: 10/05/2009] [Indexed: 10/20/2022]
Abstract
There have been relatively few studies of bone mass in children with idiopathic hypercalciuria (IH). When performed, bone mineral density (BMD) measurements have consistently disclosed decreased Z-scores for children with IH at the lumbar spine and, to a lesser extent, at the femoral neck. Few investigations have delineated the nature of the mechanism(s) that may contribute to the bone loss in these children. Some studies have been consistent, showing increased bone resorption as the probable mechanism of bone loss. To date, there have been no reports regarding the assessment of biochemical markers specific for bone formation in children with IH. However, since most of the children with IH in these reports had demonstrated normal longitudinal growth, it seems less likely that there is an alteration in bone formation. The causes for increased bone resorption also are not firmly established, but genetics, dietary indiscretions, and altered cytokine production have been proposed as being contributory to the decreased BMD observed in these children with IH. Optimal bone mineral accretion during childhood and adolescence is important in attaining peak bone mass and may serve to prevent the development of osteoporosis in adulthood. Thus, a better understanding of bone loss in children with IH is warranted.
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Affiliation(s)
- Joseph E Zerwekh
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8885, USA.
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Abstract
PURPOSE OF REVIEW In this review, recent advances in the epidemiology, genetics, clinical associations and management of idiopathic hypercalciuria will be discussed. RECENT FINDINGS A significant genetic contribution exists in the pathophysiology of hypercalciuria. Although several candidate genes and genetic alterations have been proposed, identification of precise gene(s) responsible remains elusive. Decreased bone density has been increasingly associated with hypercalciuria. Recent publications have suggested that bisphosphonates may play a role in the management in patients in whom both hypercalciuria and decreased bone density are present. SUMMARY Idiopathic hypercalciuria is a common disorder in children and can present with a range of clinical presentations such as hematuria, voiding dysfunction, flank pain, abdominal pain, nephrolithiasis, urinary tract infection and decreased bone mineral density. Dietary modifications are often sufficient in the management of hypercalciuria. If the symptoms persist or a rare monogenic disorder is present, consideration should be given to medical treatment with a thiazide diuretic and/or citrate therapy.
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Abstract
In recent years the incidence of pediatric stone disease has increased several fold, mostly due to hypercalciuria and hypocitraturia. The goal of medical treatment is to protect the patient from formation of new stones and expansion of existing ones. The non-pharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. The pharmacological treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. This review discusses the current options of medical treatment of pediatric urolithiasis.
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Affiliation(s)
- Uri S Alon
- Bone and Mineral Disorders Clinic, Children's Mercy Hospital and Clinics, University of Missouri at Kansas City, 64108, USA.
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Freundlich M, Alon US. Bisphosphonates in children with hypercalciuria and reduced bone mineral density. Pediatr Nephrol 2008; 23:2215-20. [PMID: 18704505 DOI: 10.1007/s00467-008-0940-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2008] [Revised: 05/05/2008] [Accepted: 06/09/2008] [Indexed: 11/24/2022]
Abstract
Previous studies have demonstrated reduced bone mineral density (BMD) and biochemical changes of excessive bone resorption in some patients with idiopathic hypercalciuria (IH). Consequently, bisphosphonates have been successfully employed in research animals and adults with IH and reduced BMD. We evaluated the effect of treatment with bisphosphonates in seven patients ages 10-16 years with persistent IH and reduced BMD. In five children, preceding traditional therapy failed. All children received oral alendronate and one also IV Zoledronic acid for 6-18 (median 9.0, mean 10.7) months. With treatment, BMD Z scores in the lumbar spine improved from -2.0 +/- 0.3 to -0.8 +/- 0.8 (p = 0.002) and in the femoral neck from -1.8 +/- 0.4 to -0.7 +/- 0.9 (p = 0.01); urine N-telopeptides/creatinine decreased from 372 +/- 289 to 72 +/- 39 nmol/mmol (p = 0.05) and calcium/creatinine from 0.29 +/- 0.12 to 0.13 +/- 0.06 mg/mg (p = 0.009). Height Z scores, normal at baseline in all, remained unaffected, and no new stones or fractures were documented throughout the treatment period. Serum creatinine, electrolytes, calcium, phosphorus and parathyroid hormone remained normal as well. In summary, in children with IH and decreased BMD, treatment with bisphosphonates normalized urine calcium excretion, eliminated urinary symptoms, and significantly improved reduced BMD. These short-term beneficial effects indicate the need for larger prospective studies on the potential of bisphosphonates to serve as a new tool in treating children with IH and reduced BMD.
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Low bone density in children with hypercalciuria and/or nephrolithiasis. Pediatr Nephrol 2008; 23:2209-14. [PMID: 18696122 DOI: 10.1007/s00467-008-0929-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2008] [Revised: 06/12/2008] [Accepted: 06/12/2008] [Indexed: 12/16/2022]
Abstract
The objective of this study was to identify how many children with hypercalciuria and/or nephrolithiasis have a low bone density and whether the risk of low bone density can be identified by 24-h urine stone-risk profiles and/or growth parameters. A retrospective chart review was performed on 110 idiopathic hypercalciuria and/or kidney stone patients who received both a 24-h urine for stone-risk profile and a dual-energy X-ray densitometry scan. Patients were divided into low bone density vs. normal bone density groups and hypercalcuria verus nephrolithiasis groups and analyzed for differences in growth parameters, urine stone-risk profiles, and bone densities. Overall, 47% had a bone density z score < -1, and 26% had a bone density z score < -2. Patients with a low bone density had a higher body mass index and lower urine creatinine and ammonium than those with a normal bone density. Patients with nephrolithiasis had a lower bone density z score than patients with hypercalcuria and no nephrolithiasis. Clinicians should be aware of the increased incidence of low bone density in children with hypercalciuria and nephrolithiasis. The effect of hypercalciuria and nephrolithiasis treatment on bone density and the natural progression of the bone density in the studied patient population warrants further investigation.
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Olney RC, Mazur JM, Pike LM, Froyen MK, Ramirez-Garnica G, Loveless EA, Mandel DM, Hahn GA, Neal KM, Cummings RJ. Healthy children with frequent fractures: how much evaluation is needed? Pediatrics 2008; 121:890-7. [PMID: 18450891 DOI: 10.1542/peds.2007-2079] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE We performed a case-control study to determine whether occult bone disease is associated with a history of frequent fractures in children. METHODS Healthy children with > or = 2 incidences of low-energy fractures were recruited (n = 68). Children with no history of fractures served as control subjects (n = 57). Food logs, activity surveys, physical examinations, laboratory tests, and dual-energy radiographic absorptiometry were used. RESULTS Bone mineral density z scores were significantly reduced in case subjects, compared with control subjects. Three case subjects (4.3%) and 1 control subject (1.8%) had bone mineral density z scores below the expected range. Of those 4 subjects, 2 had dairy avoidance and 2 had delayed puberty. An additional case subject had evidence of vitamin D deficiency. A significant number of subjects (20% of case subjects and 23% of control subjects) had idiopathic hypercalcuria, based on 24-hour urine collections. Among the case subjects, bone mineral density z scores were significantly lower for those with idiopathic hypercalcuria. Among the control subjects, the presence of idiopathic hypercalcuria did not affect bone mineral density. The case subjects with idiopathic hypercalcuria accounted for virtually all of the differences in bone mineral density between the case and control groups. Analysis of parathyroid hormone and 1,25-dihydroxy-vitamin D levels showed that children with frequent fractures and hypercalcuria had renal hypercalcuria, whereas children with no fractures and hypercalcuria had absorptive hypercalcuria. CONCLUSIONS We identified a significant association between a history of frequent fractures and hypercalcuria in children. We propose that the appropriate screening evaluation for children who present with a history of frequent fractures consists of a dietary history targeted at calcium and vitamin D intakes, a physical examination to assess for pubertal delay, and urinary calcium concentration/creatinine ratio determination to assess for hypercalcuria. Children with abnormalities in this screening should undergo dual-energy radiographic absorptiometry and appropriate evaluation.
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Affiliation(s)
- Robert C Olney
- Division of Pediatric Endocrinology, Nemours Children's Clinic-Jacksonville, Jacksonville, FL 32207, USA.
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Seyhan S, Yavascaoglu I, Kilicarslan H, Dogan HS, Kordan Y. Association of vitamin D receptor gene Taq I polymorphism with recurrent urolithiasis in children. Int J Urol 2007; 14:1060-2. [DOI: 10.1111/j.1442-2042.2007.01899.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Binkovitz LA, Sparke P, Henwood MJ. Pediatric DXA: clinical applications. Pediatr Radiol 2007; 37:625-35. [PMID: 17431606 PMCID: PMC1950217 DOI: 10.1007/s00247-007-0450-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2006] [Revised: 02/08/2007] [Accepted: 03/01/2007] [Indexed: 11/28/2022]
Abstract
Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin D and other nutrients; hepatic and renal activation of vitamin D; normal hormone levels (thyroid, parathyroid, reproductive and growth hormones); and neuromuscular functioning with sufficient stress upon the skeleton to induce bone deposition. The presence of genetic or acquired diseases and the therapies that are used to treat them can also impact bone health. Since the introduction of clinical DXA in pediatrics in the early 1990s, there has been considerable investigation into the causes of low bone mineral density (BMD) in children. Pediatricians have also become aware of the role adequate bone mass accrual in childhood has in preventing osteoporotic fractures in late adulthood. Additionally, the availability of medications to improve BMD has increased with the development of bisphosphonates. These factors have led to the increased utilization of DXA in pediatrics. This review summarizes much of the previous research regarding BMD in children and is meant to assist radiologists and clinicians with DXA utilization and interpretation.
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Affiliation(s)
- Larry A Binkovitz
- Department of Radiology, Columbus Children's Hospital, 700 Childrens Way, Columbus, OH, USA.
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Heller HJ, Zerwekh JE, Gottschalk FA, Pak CYC. Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria. Kidney Int 2007; 71:808-15. [PMID: 17311067 DOI: 10.1038/sj.ki.5002181] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Absorptive hypercalciuria (AH), a common stone-forming condition characterized biochemically by intestinal hyperabsorption of calcium and hypercalciuria may be associated with bone loss. In AH type I (AH-1), hypercalciuria persists despite restriction in dietary calcium intake. We therefore hypothesized that the skeleton may contribute to the hypercalciuria in this subgroup of patients. Histomorphometric analysis of iliac crest biopsies were performed on nine stone-formers with AH-1 and on nine matched normal subjects. After stabilization on a stone-prevention diet, calcium homeostasis in the stone formers was then evaluated on inpatient constant metabolic diet before and after short-term blockade of bone resorption by alendronate (10 mg daily, 17 days total). Compared with controls, the stone-formers had lower indices of bone formation (osteoblast surface/bone surface 1.8+/-2.1 vs 3.0+/-1.5%, P=0.04; wall thickness 35.8+/-6.9 vs 47.2+/-7.6%, P=0.001) and relatively higher bone resorption (osteoclast surface/bone surface 0.4+/-0.2 vs 0.2+/-0.2%, P=0.05). In the stone-formers, a short-term course of alendronate treatment corrected fasting urinary calcium (0.14+/-0.06 to 0.06+/-0.04 mg Ca/mg Cr, P=0.001) and marginally reduced 24-h urinary calcium by 48 mg/day (P=0.06). Increased intestinal calcium absorption and hypercalciuria persisted, but estimated calcium balance improved (P=0.007). Our results suggest that the hypercalciuria of AH-1 originates primarily from intestinal hyperabsorption of calcium, but bone resorption in excess of bone formation may contribute.
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Affiliation(s)
- H J Heller
- Department of Internal Medicine, UT Southwestern Medical Center at Dallas, Center for Mineral Metabolism and Clinical Research, Dallas, Texas, USA
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Srivastava T, Alon US. Pathophysiology of hypercalciuria in children. Pediatr Nephrol 2007; 22:1659-73. [PMID: 17464515 PMCID: PMC6904412 DOI: 10.1007/s00467-007-0482-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2007] [Revised: 03/11/2007] [Accepted: 03/12/2007] [Indexed: 12/17/2022]
Abstract
Urinary excretion of calcium is the result of a complex interplay between three organs-namely, the gastrointestinal tract, bone, and kidney-which is finely orchestrated by multiple hormones. Hypercalciuria is believed to be a polygenic trait and is influenced significantly by diet. This paper briefly reviews calcium handling by the renal tubule in normal and in hereditary disorders as it relates to the pathophysiology of hypercalciuria. The effects of dietary sodium, potassium, protein, calcium, and phosphate on calcium excretion, and the association of hypercalciuria with bone homeostasis is discussed, leading to recommendations on means to address excessive urinary calcium excretion.
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Affiliation(s)
- Tarak Srivastava
- Section of Nephrology, Bone and Mineral Disorder Clinic, The Children’s Mercy Hospital and Clinics, University of Missouri, 2401 Gillham Road, Kansas City, MO 64108 USA
| | - Uri S. Alon
- Section of Nephrology, Bone and Mineral Disorder Clinic, The Children’s Mercy Hospital and Clinics, University of Missouri, 2401 Gillham Road, Kansas City, MO 64108 USA
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Abstract
Bone mass increases progressively during childhood, but mainly during adolescence when approximately 40% of total bone mass is accumulated. Peak bone mass is reached in late adolescence, and is a well recognised risk factor for osteoporosis later in life. Thus, increasing peak bone mass can prevent osteoporosis. The critical interpretation of bone mass measurements is a crucial factor for the diagnosis of osteopenia/osteoporosis in children and adolescents. To date, there are insufficient data to formally define osteopenia/osteoporosis in this patient group, and the guidelines used for adult patients are not applicable. In males and females aged <20 years the terminology 'low bone density for chronologic age' may be used if the Z-score is less than -2. For children and adolescents, this terminology is more appropriate than osteopenia/osteoporosis. Moreover, the T-score should not be used in children and adolescents. Many disorders, by various mechanisms, may affect the acquisition of bone mass during childhood and adolescence. Indeed, the number of disorders that have been identified as affecting bone mass in this age group is increasing as a consequence of the wide use of bone mass measurements. The increased survival of children and adolescents with chronic diseases or malignancies, as well as the use of some treatment regimens has resulted in an increase in the incidence of reduced bone mass in this age group. Experience in treating the various disorders associated with osteoporosis in childhood is limited at present. The first approach to osteoporosis management in children and adolescents should be aimed at treating the underlying disease. The use of bisphosphonates in children and adolescents with osteoporosis is increasing and their positive effect in improving bone mineral density is encouraging. Osteoporosis prevention is a key factor and it should begin in childhood. Pediatricians should have a fundamental role in the prevention of osteoporosis, suggesting strategies to achieve an optimal peak bone mass.
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Penido MGMG, Lima EM, Souto MFO, Marino VSP, Tupinambá ALF, França A. Hypocitraturia: a risk factor for reduced bone mineral density in idiopathic hypercalciuria? Pediatr Nephrol 2006; 21:74-8. [PMID: 16252112 DOI: 10.1007/s00467-005-2035-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2005] [Revised: 06/13/2005] [Accepted: 06/15/2005] [Indexed: 01/27/2023]
Abstract
UNLABELLED The association between idiopathic hypercalciuria (IH) and reduced bone mineral density (BMD) has been described in adults and children. Frequently, hypocitraturia (HC) is an associated condition. To determine the effect that HC may have on bone metabolism of these patients, we studied 88 children with IH at diagnosis, divided into the following groups: group 1-44 (50%) patients with associated HC; group 2-44 (50%) patients without HC; group 3 (29 subjects), a healthy control group. Urinary and blood electrolytes, as long as urinary N-telopeptide, were measured. Lumbar spine (L2-L4) and femoral neck bone mineral density (BMD) and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry. There was no difference in age between the three groups (P=0.80), but weight, height, body mass index, and bone age were lower (P<0.01) and serum intact parathyroid hormone (iPTH) was higher (P<0.05) in group 1 than in groups 2 and 3. N-telopeptide, measured in urine, did not differ between groups. The following bone densitometry parameters: lumbar spine BMC, BMC adjusted for height (BMCh), BMC adjusted for width of vertebrae (BMCw) and BMD, as well as femoral neck BMD, were significantly lower in group 1 than in groups 2 and 3 (P<0.01). When we corrected densitometry parameters for height, BMC was lower in group 1 and not in group 2 when compared with controls. CONCLUSIONS Children with IH and associated HC may have a higher risk of bone mass loss and consequent osteopenia. Further studies are needed to assess the role that hypocitraturia may have in this form of bone disease.
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Skalova S, Palicka V, Kutilek S. Bone mineral density and urinary N-acetyl-beta-D-glucosaminidase activity in paediatric patients with idiopathic hypercalciuria. Nephrology (Carlton) 2005; 10:99-102. [PMID: 15877664 DOI: 10.1111/j.1440-1797.2005.00381.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after correction of dietary inbalances and has no detectable causes. Patients with IH have a higher prevalence of osteoporosis. Defective reabsorption of calcium by the renal tubule is considered a likely mechanism of IH. N-acetyl-beta-D-glucosaminidase (NAG) is a lysosomal enzyme that is a very sensitive marker of renal tubular impairment. METHODS Fifteen patients (nine boys and six girls, mean age 12.4 +/- 4.0 years) with IH (urinary calcium excretion >0.1 mmol/kg per 24 h) had their bodyweight, height, body mass index (BMI), urinary NAG/creatinine ratio (U-NAG/Cr) and 24-h urinary calcium excretion (U-Ca/24 h) assessed. L1-L4 bone mineral density (BMD) was measured by dual energy X-ray absorptiometry and volumetric BMD (BMDvol) was calculated. The obtained results were expressed as Z-scores. RESULTS The values of basic anthropometric parameters did not differ significantly from the values of the reference population and there was a tendency to short stature, which did not reach statistical significance (P = 0.08). The values of calciuria and U-NAG/Cr were significantly higher while BMD was significantly lower when compared to the reference values (P < 0.0006, P < 0.006 and P < 0.001, respectively). Inverse and significant correlations were found between U-Ca/24 h and BMD, U-Ca/24 h and body height, and U-Ca/24 h and BMDvol (r = -0.64 and -0.70, respectively, P < 0.01; r = -0.55, P < 0.05), while there was no correlation between U-NAG/Cr and U-Ca/24 h, nor between BMD and weight or BMD and BMI. CONCLUSION Tubular impairment is highly probable in children with IH, but there is a poor relationship with the degree of calcium leakage. Idiopathic hypercalciuria should be considered as a risk factor for stunted growth and low bone mass.
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Affiliation(s)
- Sylva Skalova
- Department of Paediatrics, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic
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Rodríguez-Soriano J, Vallo A, Aguirre M. Bone mineral density and bone turnover in patients with Bartter syndrome. Pediatr Nephrol 2005; 20:1120-5. [PMID: 15942790 DOI: 10.1007/s00467-005-1901-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2004] [Revised: 02/08/2005] [Accepted: 02/08/2005] [Indexed: 11/26/2022]
Abstract
The aim of this investigation was to evaluate bone mineral density (BMD), by use of DXA, and bone turnover, in patients with Bartter syndrome (BS). Ten patients (2 with BS type II and 8 with BS type III) were included in the procedure. Age at study varied between 2 and 30 years. During the studies usual treatment with indomethacin, spironolactone, and potassium chloride was maintained. Results were compared with those obtained in the 20 asymptomatic parents. Height of the patients at the time of the study did not differ from reference values (Z-score -1.2 to +0.8). Three patients (1 with BS type II and 2 with BS type III) presented reduced lumbar spine BMD or overt osteopenia (BMD Z-scores: -2.3, -1.3, and -1.1). BMD did not correlate significantly with age. Paternal and maternal femoral neck BMD values correlated significantly with lumbar spine BMD of the patients (r=0.65, P<0.05, and r=0.80, P<0.01). Lumbar spine BMD Z-scores correlated negatively with urinary Ca excretion when values both from patients and parents were jointly analyzed (r=-0.43, P<0.05). Plasma calcium concentration was significantly higher (P<0.001) and plasma phosphate Z-score was significantly lower (P<0.05) in the patients than in the parents. However, no significant differences were observed in values for intact PTH, 1,25 (OH)(2)D(3) and 25 (OH)D(3). Intact PTH values correlated positively with BMD Z-scores at lumbar spine (r=0.45, P<0.05) and at femoral neck (r=0.63, P<0.01). Age-corrected biochemical markers of bone formation (plasma alkaline phosphatase and osteocalcin concentrations) were normal whereas age-corrected markers of bone reabsorption (urinary PYD and DPD excretion) were significantly higher than parental values (P<0.01 and <0.05, respectively). We conclude that: (1) reduced BMD is not an exclusive feature of neonatal BS and it can be also observed in classic BS; (2) the loss of bone mineral is not progressive, probably because of the hypocalciuric effect of indomethacin therapy; and (3) this study did not determine whether loss of bone mass is the cause or the consequence of hypercalciuria although the beneficial effect of indomethacin therapy implies the latter.
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Affiliation(s)
- Juan Rodríguez-Soriano
- Division of Pediatric Nephrology, Department of Pediatrics, Hospital de Cruces and Basque University School of Medicine, Bilbao, Spain.
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Vezzoli G, Rubinacci A, Bianchin C, Arcidiacono T, Giambona S, Mignogna G, Fochesato E, Terranegra A, Cusi D, Soldati L. Intestinal calcium absorption is associated with bone mass in stone-forming women with idiopathic hypercalciuria. Am J Kidney Dis 2004; 42:1177-83. [PMID: 14655189 DOI: 10.1053/j.ajkd.2003.08.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Patients with idiopathic hypercalciuria are predisposed to osteoporosis despite their high enteral calcium absorption. Conversely, low calcium absorption has been reported in patients with osteoporosis. Because bone loss occurs earlier in women, this work explores the relationship between bone mineral density (BMD) and calcium absorption in premenopausal and postmenopausal hypercalciuric stone-forming women. METHODS BMD and intestinal calcium absorption were compared in 64 hypercalciuric and 42 normocalciuric calcium stone-forming women. Calcium absorption was assessed by using strontium as a surrogate marker for calcium. Strontium was administered to patients as an oral load, then measured in blood to calculate absorption after 60 minutes. Femoral and lumbar-spine BMD were measured by dual-energy x-ray absorptiometry. RESULTS Strontium absorption was significantly increased in hypercalciuric stone formers, whereas BMD z score was decreased in hypercalciuric patients at the lumbar spine, but not the femur. The increase in strontium absorption was detected in both postmenopausal (n = 29) and premenopausal (n = 35) hypercalciuric patients. The decrease in lumbar-spine BMD was confirmed in postmenopausal, but not premenopausal, hypercalciuric patients. Strontium absorption was greater in hypercalciuric patients with a lumbar-spine BMD z score of -2 or less (n = 10) than in those with a score greater than -2 (n = 54). Multiple stepwise regression showed that lumbar-spine BMD was related negatively to intestinal strontium absorption and age in hypercalciuric patients. CONCLUSION Results of the strontium absorption test suggest that the increase in calcium absorption is associated with a decrease in lumbar-spine BMD in hypercalciuric stone-forming women. Hypercalciuric stone-forming women with high calcium intestinal absorption denote a group of patients predisposed to loss of bone mass.
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Affiliation(s)
- Giuseppe Vezzoli
- Division of Nephrology, Dialysis, and Hypertension, IRCCS San Raffaele Hospital and Postgraduate School of Nephrology, Milan, Italy.
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