Teriparatide followed by antiresorptive therapy exhibits fracture reduction efficacy for up to 2 years, but it remains unclear if this leads to sustained increases in bone mineral density (BMD) and trabecular bone score (TBS), and if BMD correlates with fracture risk reduction.

In this multicenter cohort study, the effect of teriparatide administration for 18-24 months, followed by antiresorptive therapy, was assessed in patients partipicipating in a nationwide Swiss osteoporosis registry. BMD and TBS were measured up to 10 years before and after teriparatide initiation.

A total of 624 patients (87 % female, age 67 ± 13 years) were enrolled from May 2004 to December 2023. Among them, 198 (32 %) received no treatment prior to teriparatide, while 426 had received previous antiresorptive therapies (median duration 5.9 years [2.2, 8.0]). All patients underwent subsequent antiresorptive therapy, mainly with bisphosphonates and denosumab. The incidences of vertebral, hip, and any fractures were 0.96, 0.11, and 1.37, respectively, within 2 years prior to teriparatide initiation. The total hip T-score did not correlate with fracture reduction under teriparatide. After transitioning from teriparatide to an antiresorptive regimen, fracture incidence remained low and BMD was significantly higher for up to 5 years after teriparatide compared to the pre-treatment period (T-score + 0.876 for lumbar spine, p < 0.001; and + 0.112 for total hip, p < 0.005), while TBS increased by 0.047 (p < 0.001). Overall, significant improvement was observed in pretreated and treatment-naïve patients undergoing teriparatide treatment.

Teriparatide led to sustained lower incidences of vertebral, hip, and other fractures for up to 8 years after switching to antiresorptive agents in both pretreated and treatment-naïve patients. Additionally, BMD and TBS levels were significantly higher than those before teriparatide treatment. During teriparatide treatment, the total hip T-score did not correlate with fracture risk.

Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.

Osteoporosis is a national health priority, and over six million Australians over the age of 50 years have poor bone health. Fragility fractures due to osteoporosis are associated with an increased morbidity and mortality risk and a high economic cost to the community. It is a chronic condition requiring long-term management. Despite notable advances in pharmacotherapy, large treatment gaps remain. Antiresorptive drugs have been the foundation of treatment; however, their efficacy wanes and rare adverse effects accumulate with prolonged use. Osteoanabolic drugs form new bone and can also restore deteriorated bone microarchitecture, in addition to increasing bone mineral density. Currently, antiresorptive drugs are used as first-line drugs for osteoporosis. However, recent studies have highlighted the superiority of anabolic drugs for fracture reduction over antiresorptives. Furthermore, for patients at very high risk or imminent risk of fracture, the use of sequential therapy with an osteoanabolic medication followed by an antiresorptive is superior to achieving optimal long-term bone health outcomes. This article will discuss the evidence supporting the anti-fracture benefits of osteoanabolic drugs, emphasising their benefits as first-line agents for osteoporosis. Challenges surrounding transitions between osteoanabolic and antiresorptive medications are also discussed, highlighting considerations for the optimal treatment sequence with a focus on recent updates to Australian prescribing recommendations and PBS requirements.

Osteoporosis is a chronic metabolic bone disease characterized by progressive bone loss and structural deterioration, increasing fracture risk and morbidity. As the global population ages, its incidence is rising, underscoring the urgent need for more effective prevention and treatment strategies.

This review synthesizes the latest evidence and guidelines from leading international societies, establishing a contemporary framework for osteoporosis pharmacotherapy. It emphasizes best practices and explores future directions in treatment optimization and fracture prevention.

To optimize outcomes, enhancing early detection, refining treatment strategies, and prioritizing patient-centered care are essential. Improving diagnosis through increased use of bone mineral density (BMD) assessments and identifying secondary causes are critical steps to addressing underdiagnosis, particularly in men. Pharmacotherapies play a vital role in management; while bisphosphonates serve as a cost-effective first-line treatment, denosumab and anabolic agents like Teriparatide and romosozumab are essential alternatives for high-risk patients. Future directions in osteoporosis management emphasize advancing treatment strategies through novel drug targets and innovative delivery systems, alongside personalized medicine approaches considering individual genetic and comorbidity profiles. Enhanced adherence strategies and further research into combination therapies and monitoring tools are crucial for improving prevention and treatment outcomes, ultimately reducing the fragility fracture burden worldwide.

This comprehensive meta-analysis aimed to elucidate the effects of anti-osteoporosis (OP) drugs in patients who experienced rotator cuff tears and underwent arthroscopic repair.

The PubMed, Embase, Web of Science, and Cochrane Central databases were searched to identify studies that examined the effects of anti-OP drugs among patients with rotator cuff tears who underwent arthroscopic rotator cuff repair. Specifically, studies that evaluated the retear rate and other subjective or objective outcomes were included in the analysis. The databases were searched from inception to January 13, 2025.

Ultimately, 5 articles were included in this meta-analysis. Compared with the control group, the anti-OP drug group had a lower retear rate, higher American Shoulder and Elbow Surgeon scores and a greater internal rotation angle. The Simple Shoulder Test, University of California, Los Angeles shoulder score, Constant Shoulder score, and forward flexion angle were not markedly different between the two groups.

Anti-OP drugs markedly promoted bone-to-tendon healing and improved quality of life among patients who underwent arthroscopic rotator cuff repair, especially with respect to activities that involve internal rotation of the shoulder.

Cystic fibrosis-related bone disease (CFBD) is a common endocrinopathy in people living with cystic fibrosis (CF) that is complex and multifactorial in origin. People with CF experience high rates of progressive bone density loss and increased fracture risk. Focus on prevention and treatment of CFBD is of increasing importance in a now aging CF population. This review will discuss current practices in CFBD, gaps in knowledge, and potential future studies with the goal of advancing the clinical care of patients with CFBD.

Parathyroid hormone (PTH) increases bone mass and decreases fracture risk. However, the anabolic effects of PTH are limited to a period of approximately 24 months, motivating the need to maximize bone growth during this timeframe. Concurrent mechanical loading with weight-bearing exercise is synergistic with PTH treatment. We sought to determine if priming with PTH prior to initiating mechanical loading would enhance their synergistic effects. We pre-treated 10-week-old, female C57Bl/6J mice with either PTH or saline vehicle (VEH) for six weeks. We subsequently initiated cyclic tibial compression for either two or six weeks while continuing PTH or VEH treatment. We analyzed bone morphology in cortical and cancellous compartments of the proximal tibia. To further explore the effects of PTH and loading in cancellous bone, we measured bone cell presence and changes in bone morphology via histology, immunohistochemistry, and dynamic histomorphometry. Concurrent treatment with PTH enhanced load-induced increases in bone mass in cortical bone but blunted the effects of loading in cancellous bone. PTH pre-treatment further increased load-induced changes in cortical bone mass and rescued the load effects in cancellous bone, returning values to those of VEH-treated animals. Osteoclast populations decreased with loading, independent of PTH treatment. Active osteoblast populations increased with PTH pre-treatment but did not change with loading. Bone formation rate increased with PTH pre-treatment in the 2-week group but did not differ between treatment groups after 6-weeks. Collectively, pre-treating with PTH prior to mechanical loading primed the skeletal tissue and enhanced the anabolic response of concurrent treatment and loading.

By 2050, the global aging population is predicted to reach 1.5 billion, highlighting the need to enhance the quality of life of the elderly population. Osteoporotic fractures are projected to affect one in three women and one in five men over age 50. Initial treatments for osteoporosis in postmenopausal women include antiresorptive agents such as bisphosphonates, strontium ranelate, estrogen replacement therapy (ERT) and selective estrogen receptor modulators (SERMs). However, these do not rebuild bone, limiting their effectiveness. Denosumab, an FDA-approved antiresorptive monoclonal antibody, also has drawbacks including high costs, biannual subcutaneous injections, slow healing, impaired bone growth and side effects like eczema, flatulence, cellulitis, osteonecrosis of the jaw (ONJ) and an increased risk of spinal fractures after discontinuation of treatment. Nutraceuticals, particularly phytoestrogens, are gaining attention for their health benefits and safety in osteoporosis prevention, management and treatment. Phytoestrogens are plant metabolites similar to mammalian estrogens and include isoflavones, coumestans, lignans, stilbenes, and flavonoids. They interact with estrogen receptor isoforms ERα and ERβ, acting as agonists or antagonists based on concentration and bioavailability. Their tissue-selective activities are particularly significant: anti-estrogenic effects in reproductive tissues may lower the risk of hormone-related cancers (such as ovarian, uterine, breast and prostate), while estrogenic effects on bone could contribute to the preservation of bone mineral density.Phytoestrogens are, thus, used in managing breast and prostate cancers, cardiovascular diseases, menopause and osteoporosis. The present review focuses on the botanical origin, classification, sources and mechanism(s) of action of major phytoestrogens, their potential in prevention and management of osteoporosis and the requirement for additional clinical trials to achieve more definitive outcomes in order to confirm their efficacy and dosage safety.

Osteoporosis requires life-long management. This involves the use of different drugs in various sequences followed by long-term maintenance therapy. This review highlights the important transitions among osteoporosis therapies and outlines a strategy of intermittent bisphosphonate therapy for long-term maintenance.

Over the past few years, the effects and limitations of long-term treatment with bisphosphonates and denosumab have become apparent as have several key factors in the sequential use of anti-remodeling drugs and osteoanabolic agents. Strategies for transitions from estrogen, bisphosphonates, denosumab and the bone-forming drugs will be discussed, based on extant evidence, clinical experience and expert opinion. By appropriate selection of both the initial and subsequent drugs for the prevention and treatment of osteoporosis, therapeutic benefits can be optimized and safety issues minimized. Developing a strategy for long-term maintenance of the benefits of the initial therapies can provide a life plan for managing patients with osteoporosis.

Obesity, a multifactorial disease linked to severe health risks, requires innovative treatments beyond lifestyle changes and current medications. Existing anti-obesity drugs face limitations regarding efficacy, side effects, weight regain and high costs. Artificial intelligence (AI) is emerging as a pivotal tool in drug discovery, expediting the identification of novel drug candidates and optimizing treatment strategies. This review examines AI's potential in developing next-generation anti-obesity therapeutics, with a focus on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and their role in discovering anti-obesity peptides. Additionally, it explores integration challenges and offers future perspectives on leveraging AI to reshape the landscape of anti-obesity drug discovery.

The present systematic review investigates whether different doses of vitamin D and calcium supplementation in women with postmenopausal osteoporosis undergoing antiresorptive therapy have an association with BMD (spine, hip, femur neck), serum markers of osteoporosis (bone-ALP, NTX, CTX), the rate of pathological vertebral and non-vertebral fractures, adverse events, and mortality. This systematic review was conducted according to the PRISMA 2020 guidelines. PubMed, Google Scholar, Embase, and Scopus databases were accessed in September 2024. All randomised clinical trials (RCTs) comparing two or more treatments for postmenopausal osteoporosis supplemented with vitamin D and/or calcium were accessed. Only studies that indicated daily vitamin D and/or calcium supplementation doses were accessed. Data from 37 RCTs (43,397 patients) were retrieved. Patients received a mean of 833.6 ± 224.0 mg and 92.8 ± 228.7 UI of calcium and vitamin D supplementation, respectively. The mean length of the follow-up was 25.8 ± 13.3 months. The mean age of the patients was 66.4 ± 5.6 years, and the mean BMI was 25.2 ± 1.6 kg/m2. There was evidence of a statistically significant negative association between daily vitamin D supplementation and gastrointestinal adverse events (r = - 0.5; P = 0.02) and mortality (r = - 0.7; P = 0.03). No additional statistically significant associations were evidenced. In postmenopausal women who undergo antiresorptive treatment for osteoporosis, vitamin D was associated with a lower frequency of gastrointestinal adverse events and mortality. Calcium supplementation did not evidence an association with any of the endpoints of interest.Level of evidence Level I, systematic review of RCTs.

Osteoporosis, defined by reduced bone mineral density and macro- and micro-architectural degradation, leads to increased fracture risk, particularly in aging populations. While randomized controlled trials (RCTs) demonstrate that PTH1 receptor agonists, teriparatide and abaloparatide, are effective at reducing fracture risk, real-world evidence (RWE) remains sparse. This study reviews and compares the anti-fracture efficacy of these agents, against each other and against other osteoporosis treatments using both RCTs and RWE. We systematically searched Medline, Embase, and Cochrane up to May 2024, focusing on RCTs and RWE studies reporting reduction in vertebral, non-vertebral, hip, or all fractures as primary endpoint. A network meta-analysis (NMA) was conducted, first through pairwise meta-analyses of teriparatide versus abaloparatide, then a Bayesian NMA comparing each to other treatments. Safety assessments included adverse events classified by MedDRA, with a particular attention to hypercalcemia and cardiac events. Seventeen studies (11 RCTs, 6 RWE) met inclusion criteria. Teriparatide and abaloparatide were effective in reducing vertebral and non-vertebral fractures in all pairwise meta-analyses versus placebo. Abaloparatide showed an advantage over teriparatide for non-vertebral fractures (OR: 0.87, 95% CI: 0.80-0.95) and hip fractures (OR: 0.81, 95% CI: 0.71-0.93). In the NMA model, teriparatide and abaloparatide were superior to placebo, raloxifene, and calcitonin in reducing vertebral fracture while teriparatide was further superior to denosumab and risedronate. For non-vertebral fracture, abaloparatide was better than any other treatment while teriparatide was only superior to alendronate or placebo. PTH1 analogs were better than placebo at reducing all fractures while no difference was observed for the risk of hip fracture. Both abaloparatide and teriparatide demonstrate comparable safety to other osteoporosis treatments, with no increased cardiovascular risk. This review highlights that PTH1 receptor agonists effectively reduce fracture risk, with abaloparatide offering enhanced benefits for non-vertebral and hip fractures compared to teriparatide. Both agents exhibit acceptable safety profiles, suggesting their valuable role in managing osteoporosis, particularly for high-risk patients.

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility due to reduced bone quality, often accompanied by low bone mass, recurrent fractures, hearing loss, skeletal abnormalities, and short stature. Pathogenic variants in over 20 genes lead to clinical and genetic variability in OI, resulting in diverse symptoms and severity. Current management involves a multidisciplinary approach, including antiresorptive medications, physiotherapy, occupational therapy, and orthopedic surgery, which provide symptomatic relief but no cure. Advancements in gene therapy technologies and stem cell therapies offer promising prospects for long-lasting or permanent solutions. This review provides a comprehensive overview of OI's classification, pathogenesis, and current treatment options. It also explores emerging biotechnologies for stem cells and gene-targeted therapies in OI. The potential of these innovative therapies and their clinical implementation challenges are evaluated, focusing on their imminent success in treating bone disorders.

Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.

Osteoporosis treatments reduce fracture risk but cannot fully eliminate it, and the concept of treatment failure (TF) or inadequate clinical response (ICR) remains debated.

The TAILOR study aims to assess the prevalence of ICR and TF in osteoporotic women undergoing active drug treatment for postmenopausal osteoporosis.

TAILOR is a retrospective study conducted in an Italian outpatient service. We included 415 patients with at least 12 months of treatment and up to 10 years, examining clinical characteristics predicting TF and ICR. TF was defined as the occurrence of two fragility fractures while on treatment or one fracture plus lack of variation BMD and ICR as the occurrence of a new osteoporotic fracture in treated patients according to previous literature.

Seventy-two patients experienced fractures during the follow-up, of those, 26 (36%) were classified as TF. The clinical characteristics of patients with fractures were similar to those without, except for a longer postmenopausal period and lower lumbar spine bone mineral density (BMD). Postmenopausal period was significantly longer in TF compared to ICR patients. However, no significant differences were found in baseline fractures, prescribed treatments, or fracture-free survival curves with age, postmenopausal period, BMD, and previous treatments. The clinical follow-up was longer in ICR and TF patients.

TAILOR shows a higher prevalence of ICR and TF (17.3%) compared to randomized controlled trials and real-world data, with 36% of fractures during follow-up classified as TF. Clinician decisions often led to changes in antiosteoporosis treatment, particularly in TF cases, though TF diagnosis was rarely cited explicitly in medical records.

TAILOR emphasizes that common clinical factors do not reliably predict ICR and TF. The findings highlight the complexity of determining an algorithm for the best treatment approach to prevent TF and ICR.

Diabetic kidney disease is a major microvascular diabetes mellitus (DM) complication clinically associated with a gradual renal function decline. Although metformin is a common drug for managing DM, however, monotherapy treatment with any antidiabetic drug will necessitate dosage increment since type 2 DM (T2DM) deteriorates over time due to the increasing pancreatic β-cell dysfunction and will eventually require a combination therapy approach with another antidiabetic medication. Vitamin D is a food supplement that has been proven to have antidiabetic and reno-protective activities. Hence, we explore the combination of vitamin D and metformin on T2DM-induced renal dysfunction. Thirty male Wistar rats were randomized into five (5) groups: control, diabetes untreated, diabetics treated with metformin, vitamin D, and vitamin D + metformin. Vitamin D and metformin significantly reversed DM-induced hyperglycemia, electrolyte imbalance, and dyslipidemia. Also, vitamin D and metformin reversed T2DM-induced increase in serum creatinine and urea and renal lactate, LDH, and oxido-inflammatory response. These observed alterations were accompanied by an increase in proton pump activities and modulation of Nrf2/Nf-κB and XO/UA signaling. This study revealed that vitamin D and/or metformin ameliorated T2DM-induced renal injury.

➢ Skeletal stem cells (SSCs) continually replenish mature cell populations to support skeletal homeostasis.➢ SSCs repopulate by self-renewal, have multilineage potential, and are long-lived in vivo.➢ SSCs express specific combinations of cell surface markers that reflect their lineage identity.➢ SSCs adapt to their anatomic environment to support regional differences in skeletal behavior and pathology.

Osteoporosis is a chronic condition primarily affecting postmenopausal women, significantly impacting their well-being and quality of life. Traditional treatment approaches include medications, vitamins, and exercise, but there is a growing interest in alternative therapies that enhance bone health. This review was conducted by searching multiple databases, including PubMed, Medline, and Google Scholar, for studies related to osteoporosis treatment. Articles focusing on both traditional therapies such as bisphosphonates, calcium, and vitamin D supplementation, and newer advancements like vibration therapy and bone-building devices such as Osteoboost were included. Traditional treatments, such as vitamin supplementation, exercise, and bisphosphonates, remain foundational in osteoporosis management, helping to maintain bone density and reduce fracture risks. Recent developments, including vibration therapy and Osteoboost, show promising results in bone regeneration without the use of medication. While traditional therapies continue to play an essential role, advancements like vibration therapy present novel alternatives for managing osteoporosis. Further research is necessary to optimize these approaches, ensuring they maximize benefits while minimizing risks, ultimately improving patient outcomes and quality of life.

Osteoporosis is defined as a condition of increased risk of fracture due to decreased bone strength. In developed countries, the number of patients with osteoporosis and fragility fractures has been increasing in recent years due to the growing elderly population, posing a social challenge not only to fracture patients and their families but also to the social healthcare economy. Osteoporosis can be divided into two categories: primary osteoporosis caused by aging or menopause and secondary osteoporosis caused by metabolic or inflammatory diseases or drugs such as glucocorticoids. The majority of patients have primary osteoporosis, and the pathogenesis of postmenopausal osteoporosis and factors associated with fragility fractures in the elderly have been elucidated. On the other hand, rheumatoid arthritis (RA) is one of the causes of secondary osteoporosis. RA is a chronic inflammatory disease characterized by joint swelling and destruction. Most often, treatment focuses on suppressing these symptoms. However, physicians should be aware of the risk of osteoporosis in RA patients, because (1) RA is a chronic inflammatory disease, which itself can be a risk factor for osteoporosis; (2) glucocorticoids, which are sometimes administered to treat RA, can be a risk factor for osteoporosis; and (3) patients with RA are becoming older, and aging is an osteoporosis risk factor. A comprehensive understanding of the pathogenesis of osteoporosis and its fragility fractures requires elucidating the mechanisms underlying osteoclast activation, which drives their development. Furthermore, identifying the factors associated with fragility fractures is essential. This review summarizes the pathogenesis of osteoporosis, the factors associated with fragility fractures, and the associations between RA and osteoporosis development.

Through this study we aimed to present the latest and most comprehensive pooled analysis, providing an updated evaluation of the efficacy and safety of sequential therapy for primary osteoporosis, using bone formation promoters followed by bone resorption inhibitors.

PubMed, the Cochrane Library, Web of Science, and Embase databases were retrieved to identify pertinent studies. Randomized controlled trials (RCTs) on the sequential therapy of primary osteoporosis with bone formation promoters followed by bone resorption inhibitors were included. Data from clinical studies that met the eligibility criteria were extracted, and quality assessment and meta-analysis were performed using RevMan v5.4 and Stata v15.0. Sensitivity and subgroup analyses were performed to find the source of heterogeneity and discover more findings.

A total of 10 eligible articles involving 14,510 patients (7171 in the intervention group versus 7339 in the comparator group) were included for the evidence synthesis. The baseline characteristics of the two groups were similar. Pooled analysis showed that the intervention group (bone formation promoters followed by bone resorption inhibitors) increased BMD at the spine (SMD:1.64; 95% CI: 0.97, 2.31; P < 0.00001; I2 = 99%), femoral neck (SMD: 0.57; 95% CI: 0.16, 0.99; P = 0.007; I2 = 96%), and total hip (SMD: 0.82; 95% CI: 0.16, 1.48; P = 0.02; I2 = 97%) compared with the comparator group (monotherapy or combination therapy using two drugs)for postmenopausal osteoporosis patient; however, there was no statistically significant difference observed in the increase of BMD at the 1/3 distal radius comparing the intervention group and comparator group (SMD: -0.25; 95% CI: -1.49, 0.99; P = 0.069; I2 = 92%). The incidence of new fractures was reduced in the intervention group relative to the comparator group (RR: 0.60; 95% CI: 0.43, 0.82; P = 0.001; I2 = 75%). The incidence of adverse events differed statistically between the two groups (RR: 0.85; 95% CI: 0.76, 0.95; P = 0.004; I2 = 97%), but the difference in adverse event incidence was not statistically significant among subgroups within the intervention and comparator groups. The intervention group had a superiority of Clinical efficacy.

Among patients with primary osteoporosis, sequential therapy with bone formation promoters followed by bone resorption inhibitors substantially increased BMD at sites such as the spine, femoral neck, and total hip while concurrently mitigating fracture risks. However, benefits regarding BMD at the 1/3 distal radius and the incidence of adverse events have not yet been established.

Registered on PROSPERO (ID: CRD42023437188).

G protein-coupled receptors (GPCRs), the largest family of membrane receptors in the mammalian genomes, regulate almost all known physiological processes by transducing numerous extracellular stimuli including almost two-thirds of endogenous hormones and neurotransmitters. The traditional view held that GPCR signaling occurs exclusively at the cell surface, where the receptors bind with the ligands and undergo conformational changes to recruit and activate heterotrimeric G proteins. However, with the application of advanced biochemical and biophysical techniques, this conventional model is challenged by the elucidation of spatiotemporal GPCR activation with the evidence that receptors can signal from subcellular compartments to exhibit various molecular and cellular responses with physiological and pathophysiological relevance. Thus, this 'location bias' of GPCR signaling has become another layer of complexity of GPCR signal transduction. In this review, we generally introduce the development of the concept of compartmentalized GPCR signaling and comprehensively summarize the receptors reported to be localized on the membranes of different intracellular organelles. We review the physiological functions of these compartmentalized GPCRs with emphasis on some well-characterized prototypical hormone/neurotransmitter-binding receptors, including β2-adrenergic receptor, opioid receptors, parathyroid hormone type 1 receptor, thyroid-stimulating hormone receptor, cannabinoid receptor type 1, and metabotropic glutamate receptor 5, as examples. In addition, the therapeutic implications of compartmentalized GPCR signaling by introducing lipophilic or hydrophilic ligands for intracellular targeting, lipid conjugation anchor drugs, and strategy to modulate receptor internalization/resensitization, are highlighted and open new avenues in GPCR pharmacology and therapeutics.

Osteoporosis (OP) is a prevalent bone disease characterized by reduced bone density and quality, increasing fragility and fracture risk. Osteoclast (OC) activity and circadian rhythm play a role in the pathogenesis of OP. Melatonin is a circadian regulator that affects bone metabolism, but its molecular mechanism has not been studied in detail. This study aimed to identify the relationship between melatonin-related genes and OP through bioinformatics methods and to verify it experimentally.We analysed microarray data from the GSE35959 dataset, identifying differentially expressed genes in OP patients. Circadian rhythm-related genes and melatonin-related genes intersect with these differentially expressed genes, highlighting that CSNK1D is a central gene. Functional enrichment, correlation and protein-protein interaction analyses were conducted. Experimental validation involved in vitro differentiation assays using RAW264.7 cells and in vivo studies with an ovariectomy-induced rat model of OP to evaluate the role of CSNK1D in osteoclastogenesis to verify its effect on OP. Differential expression analysis revealed 272 significant genes, with CSNK1D identified as central to the circadian rhythm and to melatonin and OP interplay. Functional analyses showed involvement of CSNK1D in OC differentiation and inflammatory pathways. in vitro experiments confirmed CSNK1D upregulation during OC differentiation, and small interfering RNA-mediated knockdown reduced OC marker expression and TRAP+ cell formation. in vivo, CSNK1D expression is associated with bone loss in OP rats. Melatonin-related CSNK1D promotes OC differentiation and promotes the development of OP. These findings suggest CSNK1D as a potential therapeutic target for OP, offering insights into new treatment strategies integrating circadian rhythm regulation.

The implementation of an in-hospital fracture liaison service facilitated prompt initiation of anti-osteoporosis treatment following a hip fracture (HF), increasing follow-up and treatment rates. This led to a 48% reduction in the risk of subsequent HF and a 29% decrease in mortality rates.

To demonstrate the impact of an institutional fracture liaison service (FLS) which allowed in-hospital anti-osteoporosis treatment following hip fracture (HF) on subsequent HF and mortality rate.

We retrospectively evaluated patients aged 65 years and older, admitted with an osteoporotic HF, who were transferred following surgery for rehabilitation in the geriatrics department in two time periods: before and after the implementation of an institutional FLS ("geriatric-pre-FLS" and "geriatric-FLS" cohorts, respectively). Data were captured from electronic records and the two cohorts were compared following an assessment of baseline characteristics, follow-up, and anti-osteoporosis treatment initiation. A multivariable Cox regression model evaluated differences between the cohorts regarding subsequent HF and mortality rates.

Three hundred and eighteen and 448 patients comprised the geriatric-pre-FLS (07/2008-06/2014) and the geriatric-FLS (03/2016-03/2020) cohorts, respectively. Baseline characteristics were comparable between the cohorts (median age 81 vs. 82, p = 0.08 and female sex 73% vs. 70%, p = 0.48, respectively). Rates of endocrine consultation (3.5% vs. 99%%, p < 0.001), DXA-BMD testing (7.5% vs. 34%, p < 0.001), and parenteral anti-osteoporosis treatment (4% vs. 76.6%, p < 0.001) were all higher in the geriatric-FLS cohort. The implementation of the FLS led to a 48% reduction in subsequent HF risk (HR 0.52; 95% CI 0.37-0.74, p < 0.001) and a 29% decrease in mortality rate (HR 0.71; 95% CI 0.54-0.92, p = 0.011).

The implementation of an in-hospital FLS facilitated prompt initiation of anti-osteoporosis treatment following a HF, increased follow-up and treatment rates, and resulted in a 48% reduction in subsequent HF risk and a 29% reduction in mortality rates.

Abaloparatide and teriparatide are osteoanabolic treatments indicated for postmenopausal women and men with osteoporosis at high risk of fracture. In the Abaloparatide Comparator Trial In Vertebral Endpoints study, bone mineral density improvements were significantly greater with abaloparatide compared to teriparatide at the total hip and femoral neck. We conducted a retrospective claims study to examine the incidences of hip and nonvertebral fractures and cardiovascular events in women aged ≥50 years initiating abaloparatide or teriparatide therapy, expanding on a previous retrospective claims study.

This retrospective observational study used anonymized claims data from ICON's Symphony Health, PatientSource for women aged ≥ 50 years with ≥ 1 prescription fill for abaloparatide or teriparatide. The index date was the date of the initial prescription dispensed. Times to first hip fracture, nonvertebral fracture, and serious cardiovascular event were compared between logistic regression-based propensity score-matched cohorts and in predefined subgroups by age, prior antiresorptive use, and prior fracture using Cox proportional hazards models.

Patients (21 676 per cohort) were well matched on 73 baseline parameters. Forty-five percent of patients in the abaloparatide arm and 47% in the teriparatide arm were exposed to treatment for longer than 12 months. Over 18 months (+ 30 days follow-up), 245 (1.1%) and 296 (1.4%) women in the abaloparatide and teriparatide cohorts, respectively, had a hip fracture (HR [95% CI] 0.83 [0.70, 0.98]; P = .027); 947 (4.4%) and 1078 (5.0%) had a nonvertebral fracture (0.88 [0.80, 0.96]; P = .003). There were no significant treatment-subgroup interactions (P ≥ .2). Cardiovascular events were similar between groups.

There were significantly lower rates of hip and nonvertebral fractures with abaloparatide compared to teriparatide, which were consistent across subgroups. No differences in cardiovascular safety were noted between cohorts.

Renal osteodystrophy is commonly seen in patients with chronic kidney disease (CKD) due to disrupted mineral homeostasis. Given the impaired renal function in these patients, common antiresorptive agents, including bisphosphonates, must be used with caution or even contraindicated. Therefore, an alternative therapy without renal burden to combat renal osteodystrophy is urgently needed. Here, we report that clinically relevant aerobic exercise significantly prevents high-turnover renal osteodystrophy in CKD mice and patients with CKD without compromising renal function. Mechanistically, 4-week aerobic exercise in CKD mice increased expression of skeletal muscle PPARγ coactivator-1α (PGC-1α) and circulating irisin. Both exercise and irisin administration significantly activated osteoblasts, but not osteoclasts, via integrin αvβ5, thereby conferring bone quality benefits. Removal of irisin-influenced thermogenic adipose tissues or genetic ablation of uncoupling protein 1 did not alter the irisin-conferred antiosteodystrophy effect. Importantly, in a pilot clinical study, 12-week aerobic exercise in patients with high-grade CKD significantly increased circulating irisin and prevented osteodystrophy progression, without detectable renal burden. The combination of irisin and current antiresorptive agents effectively rescued renal osteodystrophy in mice. Our work provides mechanistic insights into the role of exercise and irisin in renal osteodystrophy, and it highlights a clinically relevant, low-cost, kidney-friendly therapy for patients with this devastating disease.

The parathyroid hormone type 1 receptor (PTH1R) plays a crucial role in modulating various physiological functions and is considered an effective therapeutic target for osteoporosis. However, a lack of detailed molecular and energetic information about PTH1R limits our comprehensive understanding of its activation process. In this study, we performed computational simulations to explore key events in the activation process, such as conformational changes in PTH1R, Gs protein coupling, and the release of guanosine diphosphate (GDP). Our analysis identified kinetic information, including the rate-determining step, transition state, and energy barriers. Free-energy and structural analyses revealed that GDP could be released from the Gs protein when the binding cavity is partially open. Additionally, we predicted important residues, including potential pathogenic mutations, and verified their significance through site-directed mutations. These findings enhance our understanding of class B GPCR activation mechanisms. Furthermore, the methodology employed in this study can be applied to other biophysical systems.

Osteoporosis is a common disease that affects approximately 6 million people in Germany alone. Osteoporotic fractures impair the quality of life and may make independent living impossible. Recommendations on the diagnosis and treatment of osteoporosis are indispensable for the effective care of this large group of patients.

For a thorough updating of the German clinical practice guideline (an evidence-based guideline with recommendations for clinical practice) on osteoporosis, a comprehensive, systematic search for relevant publications was carried out, including guidelines from other countries. The retrieved literature was assessed with standardized (Oxford) criteria, and clinically relevant key questions were answered according to the PICO scheme ("population, intervention, comparison, outcomes").

The assessment of clinical risk factors for osteoporosis is the basis of osteoporosis diagnostics, which should be carried out quickly after a fracture. If risk factors are present in a postmenopausal woman or a man aged 50 or above, bone densitometry testing with dual-energy x-ray absorptiometry (DXA) is recommended. The further diagnostic evaluation should proceed in stepwise fashion depending on the clinical symptoms, the fracture status, and the degree of bone density reduction. Pharmacotherapy should be adapted to the fracture risk. Osteoanabolic treatment is recommended with high priority if the patient is judged to have a very high risk of fracture (10% or more in the next three years). The further course and duration of treatment should be determined individually, depending on the evolution of the patient's clinical state.

Prerequisites for the optimal treatment of patients with osteoporosis include a correct diagnosis and interdisciplinary and interprofessional collaboration to determine and provide the proper treatment. 71% of persons with osteoporosis in Germany are still untreated, and this gap must be closed.

Phosphodiesterases (PDEs) have drawn attention due to their critical roles in physiological and pathological conditions. Many research groups have studied these hydrolytic enzymes to develop new drugs, including apremilast as a PDE4 inhibitor and sildenafil as a PDE5 inhibitor. Targeting PDE7 has also been deemed a rational strategy to ameliorate autoimmune conditions. However, to date, no successful clinical results have been reported. We postulated that progress in these studies with PDE7 had been hampered by the lack of a potent ligand with a reasonable selectivity for this PDE isozyme. Therefore, starting from a PDE7A/7B dual inhibitor, our investigations led to improved selectivity along with extended metabolic stability, resulting in a novel PDE7A inhibitor 26. This compound with high selectivity over the closest isozyme is an ideal chemical entity to unveil new pharmacological roles of PDE7A-dependent signaling, as exemplified by the in vivo antiosteoporotic effects.

The aim of this study was to investigate the cardiovascular safety of romosozumab in postmenopausal women with osteoporosis. Romosozumab, a monoclonal antibody targeting sclerostin, has been shown to increase bone mineral density and reduce the risk of osteoporotic fractures. However, in previous studies, romosozumab therapy was identified as a potential risk factor for cardiovascular events, particularly in patients with predisposing cardiovascular disease.

A systematic literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science databases to identify randomized controlled trials (RCTs) comparing the safety and efficacy of romosozumab versus alendronate, teriparatide, denosumab, or placebo in postmenopausal women with osteoporosis. Contrast-based network meta-analysis was performed using a random-effects model. The pooled estimates are presented as risk ratios with 95% confidence intervals.

Of the 5282 articles retrieved, 25 RCTs were included in this review (n = 24,942), and 18 randomized controlled trials (n = 16,777) were included in the network meta-analysis. The results indicated no significant differences in cardiovascular mortality rate between romosozumab and placebo. Regarding the risk of major cardiovascular events, no significant differences were found in the direct evidence or the network meta-analysis with placebo as the reference.

Romosozumab might be a safe option for treating postmenopausal women with osteoporosis. The cardiovascular concerns associated with this treatment seem less significant than previously suggested, although additional real-world data are required to confirm this conclusion.

This study aimed to assess the efficacy and safety of a combined recombinant human parathyroid hormone 1-34 [rhPTH (1-34)] and vitamin K2 therapy versus vitamin K2 alone in the treatment of postmenopausal osteoporosis. A total of 77 postmenopausal osteoporosis patients were randomly divided into two groups. Patients in one group received vitamin K2 alone, while patients in the other group received a combination of rhPTH (1-34) and vitamin K2. Bone mineral density (BMD), electrolyte levels, pain scores, bone metabolism levels, and adverse drug reactions were compared pre- and post-treatment. Both two treatments improved BMD, blood calcium concentrations, pain scores, and increased osteocalcin and osteoprotegerin levels. Notably, the combined rhPTH (1-34) and vitamin K2 treatment demonstrated superior efficacy in improving BMD and bone metabolism markers. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups, indicating the safety of the combined treatment. In summary, the combined therapy of rhPTH (1-34) and vitamin K2 exhibited more potent efficacy in the treatment of postmenopausal osteoporosis, more effectively enhancing BMD and bone metabolism markers than vitamin K2 alone, without a significant increase in adverse reactions.

In the management of osteoporosis, anti-resorptive agents serve as a primary therapeutic approach. However, in cases where individuals exhibit an increased susceptibility to fractures, such as those characterized by severe low bone mass or a history of vertebral or hip fractures that markedly diminish life expectancy, the immediate reduction of fracture risk through the administration of osteoanabolic agents could be beneficial. Teriparatide, available in daily, once-weekly, or twice-weekly dosages, along with abaloparatide and romosozumab, constitutes a trio of such agents. Each of these medications is defined by unique characteristics, distinct efficacy profiles, and specific adverse effects. There is growing evidence to suggest that these agents have a superior effect on enhancing bone mineral density and reducing fracture incidence when compared to traditional bisphosphonate therapies. Nonetheless, their employment demands thorough consideration of clinical indications, which includes evaluating economic factors, the frequency of injections required, and the potential for adverse effects. The objective of this review is to consolidate the current evidence focusing primarily on the efficacy of these agents, with the goal of enhancing understanding and aiding in making more informed treatment decisions, particularly for those individuals who are at an elevated risk of fractures.

Biosimilar products have clinical characteristics similar to those of brand-name products and can reduce medical costs. However, the use of biosimilar products for osteoporosis treatments remains limited due to concerns regarding its safety and efficacy. We aimed to clarify the effectiveness and safety of the biosimilar teriparatide compared with those of the reference product using the incidence of new fractures and osteosarcoma as outcomes in osteoporosis patients.

This study used the DeSC database, which contains medical claims data for various insurers in Japan. We included patients with osteoporosis aged ≥65 years who newly received either biosimilar teriparatide or the reference products between April 2019 and November 2022. Competing risk analyses were performed with adjustments for patient characteristics. The primary and secondary outcomes were the occurrence of new fractures and osteosarcoma, respectively.

Among 45 861 included patients, 3613 and 42 248 were in the biosimilar and reference product groups, respectively. The median follow-up duration was 439 days. New fractures occurred in 6.7% of patients. Cumulative incidence function curves showed similar risks of new fractures over time in both groups. The cause-specific hazard ratio for new fractures was 0.95 (95% confidence interval: 0.82-1.11) for the biosimilar group compared with that of the reference product group. The incidence of osteosarcoma did not differ significantly between the groups (P = .559).

The biosimilar teriparatide showed effectiveness and safety comparable with those of the reference products in treating osteoporosis patients. Our results suggest that clinicians need not hesitate to prescribe biosimilar teriparatide for osteoporosis patients.

The 24th Annual Santa Fe Bone Symposium (SFBS) was held in Santa Fe, New Mexico, USA, on August 2-3, 2024. This was a "hybrid" meeting, with in-person and real-time remote participants representing a broad range of geographical locations and medical disciplines. The focus was on new developments in the care of patients with osteoporosis, other metabolic bone diseases, and inherited skeletal disorders. The most current medical evidence was presented and discussed with consideration of implications for patient management. Topics included an update on clinical uses of osteoanabolic agents, management of patients discontinuing denosumab, bone health optimization for orthopedic surgery, estrogen and testosterone in the management of osteoporosis, osteoporosis treatment in the very old, overview of rare bone diseases, treat-to-target for osteoporosis, and a progress report on global activities of Bone Health ECHO. There were two highly interactive faculty panel discussions - one with case presentations by attendees and another with open microphone for all topics of interest. Endocrinology fellows, selected from attendees of the Santa Fe Fellows Workshop on Metabolic Bone Diseases, held the two days preceding the SFBS, participated with presentations of oral abstracts. Ancillary events addressed modern approaches to menopause and bone health, case studies of management of patients at very high fracture risk, and management of patients with rare bone diseases, such as hypophosphatasia, fibrodysplasia ossificans progressiva, X-linked hypophosphatemia, and hypoparathyroidism. These proceedings of the SFBS present the clinical highlights of the plenary sessions and the discussions that followed.

The use of medications in sequence is recommended in several osteoporosis guidelines to afford the best protection for the patient at very high risk of fracture. Sequential therapy following once-weekly as well as daily teriparatide treatment is a potent option for those patients.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) contributes substantially to the burden of cardiovascular disease and fractures in patients with CKD. An increasing arsenal of diagnostic tools, including bone turnover markers and bone imaging, is available to support clinicians in the management of CKD-associated osteoporosis. Although not mandatory, a bone biopsy remains useful in the diagnostic workup of complex cases. In this special report, the European Renal Osteodystrophy (EUROD) initiative introduces the concept of a kidney-bone multidisciplinary team (MDT) for the diagnosis and clinical management of challenging cases of CKD-associated osteoporosis. In 2021, the EUROD initiative launched virtual clinical-pathological case conferences to discuss challenging cases of patients with CKD-associated osteoporosis, in whom a bone biopsy was useful in the diagnostic workup. Out of these, we selected four representative cases and asked a kidney-bone MDT consisting of a nephrologist, an endocrinologist and a rheumatologist to provide comments on the diagnostic and therapeutic choices. These cases covered a broad spectrum of CKD-associated osteoporosis, including bone fracture in CKD G5D, post-transplant bone disease, disturbed bone mineralization, severely suppressed bone turnover and severe hyperparathyroidism. Comments from the MDT were, in most cases, complementary to each other and additive to the presented approach in the cases. The MDT approach may thus set the stage for improved diagnostics and tailored therapies in the field of CKD-associated osteoporosis. We demonstrate the clinical utility of a kidney-bone MDT for the management of patients with CKD-MBD and recommend their establishment at local, national, and international levels.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and deterioration of the microarchitecture, resulting in bone fragility and risk of fractures. As the life expectancy of the population increases, fragility fractures are expected to become more common. Indeed, the incidence rate for major fracture (hip, vertebra, pelvis, etc.) is highest among the population of adults aged 80 and over. Despite this, in Spain, three out of four patients who have experienced a fragility fracture do not receive drug treatment for the secondary prevention of new fractures. Therefore, it is crucial to raise awareness among healthcare professionals of the need to assess imminent fracture risk in older patients who have already sustained a fragility fracture and to initiate a rapid, appropriate, effective, and safe secondary fracture prevention strategy. The various clinical guidelines on secondary prevention of fragility fractures published to date do not reflect the heterogeneity of older adults. The aim of this paper is to provide a brief description of the available scientific evidence on the efficacy and safety of pharmacological treatments for osteoporosis in older adults and to submit a position paper proposed by the Spanish Society of Osteoporotic Fractures (SEFRAOS), which places greater emphasis on the specifics of the approach to and treatment of older adults who have sustained a fragility fracture.

Fragility fractures in young adults present significant clinical challenges due to the limited evidence on the effectiveness of bisphosphonates in preventing subsequent fractures.

To evaluate the effectiveness of bisphosphonate therapy in reducing the fracture risk among premenopausal women with a history of osteoporotic fractures.

A population-based retrospective cohort study was conducted using data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in South Korea, covering the years 2003 to 2014.

A nationwide healthcare setting utilizing a representative cohort database.

Among 2,087 premenopausal women with osteoporotic fractures, participants were propensity score-matched based on age and body mass index at a 1:3 ratio, resulting in 132 bisphosphonate users and 396 non-users.

Bisphosphonate treatment.

The incidence of osteoporotic fractures.

Bisphosphonate users had a significantly lower risk of major osteoporotic fractures (HR 0.618, 95% CI 0.396 - 0.963) compared to non-users. Ibandronate users showed significant reductions in both major osteoporotic (HR 0.376, 95% CI 0.164 - 0.861) and nonvertebral fractures (HR 0.214, 95% CI 0.052 - 0.877). Also, longer duration of bisphosphonate use (≥180 days) was associated with a significantly lower risk of major osteoporotic and nonvertebral fractures (HR 0.528, 95% CI 0.300 - 0.929; HR 0.409, 95% CI 0.187 - 0.895, respectively).

Bisphosphonate therapy significantly reduces fracture risk in premenopausal women with previous osteoporotic fractures, especially at higher cumulative doses. These findings support considering bisphosphonates as a treatment option in premenopausal women at high risk of fractures.

This study investigates the effects of two parathyroid hormone (PTH) analogs, rhPTH(1-34) and dimeric R25CPTH(1-34), on bone regeneration and osseointegration in a postmenopausal osteoporosis model using beagle dogs. Twelve osteoporotic female beagles were subjected to implant surgeries and assigned to one of three groups: control, rhPTH(1-34), or dimeric R25CPTH(1-34). Bone regeneration and osseointegration were evaluated after 10 weeks using micro-computed tomographic (micro-CT), histological analyses, and serum biochemical assays. Results showed that the rhPTH(1-34) group demonstrated superior improvements in bone mineral density, trabecular architecture, and osseointegration compared to controls, while the dimeric R25CPTH(1-34) group exhibited similar, though slightly less pronounced, anabolic effects. Histological and TRAP assays indicated both PTH analogs significantly enhanced bone regeneration, especially in artificially created bone defects. The findings suggest that both rhPTH(1-34) and dimeric R25CPTH(1-34) hold potential as therapeutic agents for promoting bone regeneration and improving osseointegration around implants in osteoporotic conditions, with implications for their use in bone-related pathologies and reconstructive surgeries.

Bone tissue provides structural support for our bodies, with the inner bone marrow (BM) acting as a hematopoietic organ. Within the BM tissue, two types of stem cells play crucial roles: mesenchymal stem cells (MSCs) (or skeletal stem cells) and hematopoietic stem cells (HSCs). These stem cells are intricately connected, where BM-MSCs give rise to bone-forming osteoblasts and serve as essential components in the BM microenvironment for sustaining HSCs. Despite the mid-20th century proposal of BM-MSCs, their in vivo identification remained elusive owing to a lack of tools for analyzing stemness, specifically self-renewal and multipotency. To address this challenge, Cre/loxP-based cell lineage tracing analyses are being employed. This technology facilitated the in vivo labeling of specific cells, enabling the tracking of their lineage, determining their stemness, and providing a deeper understanding of the in vivo dynamics governing stem cell populations responsible for maintaining hard tissues. This review delves into cell lineage tracing studies conducted using commonly employed genetically modified mice expressing Cre under the influence of LepR, Gli1, and Axin2 genes. These studies focus on research fields spanning long bones and oral/maxillofacial hard tissues, offering insights into the in vivo dynamics of stem cell populations crucial for hard tissue homeostasis.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis and clinical trials are ongoing to study their effectiveness in OI adults. Additionally, novel bone-protective agents are in preclinical studies and various phases of OI clinical trials. This review summarizes current knowledge on available pharmacologic agents and current drug trials involving OI participants. A PubMed online database search of all study types published in the English language using the terms "osteogenesis imperfecta," "OI," and "brittle bone disease" was performed in August 2022. Articles screened were restricted to adults. A ClinicalTrials.gov database search of all studies involving "osteogenesis imperfecta" was performed in August 2023. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving bone mineral density. As of yet, no clinical trials are available that adequately evaluate the usefulness of current therapies in reducing fracture risk. Several therapeutics, including teriparatide, setrusumab, anti-TGF-β antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade.

A retrospective analysis comparing a teriparatide biosimilar (RGB-10) with reference teriparatide for osteoporosis treatment in postmenopausal women at high fracture risk found them to be therapeutically equivalent. Both provided significant improvements in lumber spine BMD, TBS, and other parameters of bone health, assessed using multiple diagnostic methods.

To compare the therapeutic efficacy of a teriparatide biosimilar (RGB-10) with reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high fracture risk.

A retrospective analysis of 25 postmenopausal female patients treated for osteoporosis with RGB-10 for 24 months and a matched cohort of 25 patients treated with reference teriparatide. The following outcomes were assessed at baseline, 12 and 24 months: bone mineral density (BMD) at the lumbar spine, femoral neck and total hip using dual-energy x-ray absorptiometry (DXA) and integral, trabecular and cortical volumetric and surface BMD using 3D-SHAPER® imaging, trabecular bone score (TBS), quantitative ultrasound (QUS) measurements, and high-resolution peripheral quantitative computed tomography (HRpQCT) imaging of the radius and tibia.

No significant differences were observed between treatment groups in any of the measured parameters of BMD or bone health at baseline as well as in any timepoint when assessed using these various diagnostic methods. Both compounds provided equivalent significant improvements from baseline in measures of osteoporosis and fracture risk.

The results of the analysis demonstrate the therapeutic equivalence of the teriparatide biosimilar (RGB-10) to reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high risk of fracture.