• Bibliometric analysis
• Femoral shaft fractures
• Femur
• Trauma
• Treatment outcomes

• Bone remodeling
• Femoral diaphysis
• PDGF-BB
• SAON

• atypical femur fracture
• bisphosphonates
• osteoporosis
• rehabilitation

• dynamic intramedullary nailing
• femur fractures
• static intramedullary nailing
• tibia fractures

• FOXA1
• Human PPI network
• Machine learning
• Osteogenic differentiation
• Osteoporosis
• hBMSCs
• mBMSCs

• Hepatocyte Nuclear Factor 3-alpha/genetics
• Hepatocyte Nuclear Factor 3-alpha/metabolism
• Animals
• Ovariectomy/adverse effects
• Osteogenesis/genetics
• MAP Kinase Signaling System
• Female
• Mice
• Osteoporosis/metabolism
• Osteoporosis/genetics
• Osteoporosis/etiology
• Osteoporosis/prevention & control
• Cell Differentiation/genetics
• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/cytology
• Gene Knockdown Techniques
• Humans
• Disease Models, Animal

• No.2021KY939 Medical Health Science and Technology Project of Zhejiang Provincial Health Commission

• Alternative medicine
• Ayurvedic
• Complementary medicine
• Herbal
• Indian medicine
• Non-allopathic
• Osteoporosis
• The natural approach to osteoporosis
• Traditional systems of medicine

• atypical fractures
• bisphosphonates
• bone mineral density
• femur fractures
• metabolic bone disease

• Female
• Humans
• Middle Aged
• Diphosphonates/adverse effects
• Alendronate/adverse effects
• Osteoporosis, Postmenopausal/complications
• Osteoporosis, Postmenopausal/drug therapy
• Osteoporosis, Postmenopausal/chemically induced
• Bone Density Conservation Agents/adverse effects
• Mandibular Fractures/surgery
• Mandibular Fractures/chemically induced
• Mandibular Fractures/drug therapy
• Osteoporosis/chemically induced
• Osteoporosis/drug therapy
• Fractures, Spontaneous/chemically induced
• Fractures, Spontaneous/diagnostic imaging
• Femoral Fractures/chemically induced
• Femoral Fractures/surgery
• Osteomyelitis/drug therapy

• Humans
• Proteome/analysis
• Proteomics/methods
• Hydroxyproline
• Bone and Bones/metabolism
• Osteoarthritis/metabolism
• Collagen

• R01 DE019284 NIDCR NIH HHS
• T32 AG000266 NIA NIH HHS
• S10 OD028654 NIH HHS
• U01 AG060906 NIA NIH HHS
• R21 AR083065 NIAMS NIH HHS
• NIH/NIA
• NIH
• Glenn Foundation
• Forever Healthy

• bone homeostasis
• cellular mechanisms
• cytokines
• hormones
• models
• osteoporosis
• pathophysiology

• Humans
• Pathology, Molecular
• Osteoporosis/therapy
• Osteoporosis/drug therapy
• Osteoporotic Fractures
• Bone Density
• Bone and Bones

• Bisphosphonate
• COVID-19
• epidemiology
• global health
• human
• medicine
• retrospective cohort study

• Humans
• COVID-19/epidemiology
• Diphosphonates/therapeutic use
• COVID-19 Testing
• SARS-CoV-2
• Retrospective Studies
• COVID-19 Vaccines
• Prospective Studies
• Respiratory Tract Infections/drug therapy
• Bronchitis/drug therapy

• CRI2453 Cancer Research Institute
• R01 AI155865 NIAID NIH HHS
• R01 AR068383 NIAMS NIH HHS
• R01 AI175379 NIAID NIH HHS
• AR068383 NIAMS NIH HHS
• National Institute of Allergy and Infectious Diseases
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
• MassCPR

• Epidemiology
• Incidence
• Osteosynthesis
• Trauma
• Trochanteric fractures

• Female
• Humans
• Male
• Femoral Fractures
• Germany/epidemiology
• Hip Fractures/epidemiology
• Hip Fractures/surgery
• Quality of Life
• Middle Aged
• Aged
• Aged, 80 and over

• Universität zu Lübeck (3165)

• Atypical femoral fracture
• Bisphosphonate
• Dynamic locking
• Dynamisation
• Intramedullary nail

• Atypical fracture
• Atypical tibia fracture
• Breast cancer
• Denosumab
• Metastatic bone disease
• Skeletal-related events

• Bisphosphonates
• Bone disease
• Denosumab
• Myeloma
• Osteoblast
• Osteoclasts

• Atypical stress fractures
• bisphosphonate use
• magnetic resonance imaging

• complication
• conventional femoral nail
• distal locking
• stabilite
• femoral shaft fracture
• functional outcome
• malunion
• radiological outcome
• talon femoral nail

• Adult
• Aged
• Female
• Femoral Fractures/diagnostic imaging
• Femoral Fractures/surgery
• Femur
• Fracture Fixation, Intramedullary/methods
• Humans
• Male
• Middle Aged
• Osteoarthritis
• Retrospective Studies
• Young Adult

Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1β, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP.

Bisphosphonates are commonly used in the treatment of osteoporosis. Atypical femoral fracture (AFF) is a well-known adverse effect of bisphosphonate use. The importance of genetic factors has been demonstrated in bone quality, bone turnover, and in the response to osteoporosis treatment. Herein, we present two cases of bilateral AFFs after bisphosphonate use for a short period of time in members of the same family (mother and her daughter) and discuss genetic predisposition to bisphosphonate-induced AFFs in the light of literature data.

• Atypical femoral fracture
• bisphosphonate
• genetic factors

• ATYPICAL FEMUR FRACTURE
• BISPHOSPHONATES
• HRQOL
• OSTEOPOROSIS
• QUALITY OF LIFE
• SF‐36

• Breast cancer
• Elderly
• Screening
• Treatment

• Dorsolumbar vertebrae
• insufficiency fracture
• osteoporosis
• talus fracture
• technetium-99m methylene diphosphonate bone scan

• extracellular vesicles
• human adipose tissue-derived stem cells
• let-7b-5p
• miR-21-5p
• osteoporosis
• osteoprotegerin

• Adipose Tissue/metabolism
• Animals
• Disease Models, Animal
• Extracellular Vesicles/metabolism
• Female
• Humans
• Mice
• Osteoporosis/pathology
• Osteoporosis/therapy
• Osteoprotegerin/genetics
• Stem Cells/metabolism

• National Research Foundation
• Ministry of Food and Drug Safety
• Ministry of Education

Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis. Bisphosphonates function by binding to hydroxyapatite, and subsequently targeting osteoclasts by altering their ability to resorb and remodel bone. Whilst aiming to reduce the risk of fragility fractures, bisphosphonates have been associated with atypical insufficiency fractures, specifically in the femur. Atypical femoral fractures occur distal to the lesser trochanter, until the supracondylar flare. There are a number of the differing clinical and radiological features between atypical femoral fractures and osteoporotic femoral fractures, indicating that there is a distinct difference in the respective underlying pathophysiology. At the point of presentation of an atypical femoral fracture, bisphosphonate should be discontinued. This is due to the proposed inhibition of osteoclasts and apoptosis, resulting in impaired callus healing. Conservative management consists primarily of cessation of bisphosphonate therapy and partial weightbearing activity. Nutritional deficiencies should be investigated and appropriately corrected, most notably dietary calcium and vitamin D. Currently there is no established treatment guidelines for either complete or incomplete fractures. There is agreement in the literature that nonoperative management of bisphosphonate-associated femoral fractures conveys poor outcomes. Currently, the favoured methods of surgical fixation are cephalomedullary nailing and plate fixation. Newer techniques advocate the use of both modalities as it gives the plate advantage of best reducing the fracture and compressing the lateral cortex, with the support of the intramedullary nail to stabilise an atypical fracture with increased ability to load-share, and a reduced bending moment across the fracture site. The evidence suggests that cephalomedullary nailing of the fracture has lower revision rates. However, it is important to appreciate that the anatomical location and patient factors may not always allow for this. Although causation between bisphosphonates and atypical fractures is yet to be demonstrated, there is a growing evidence base to suggest a higher incidence to atypical femoral fractures in patients who take bisphosphonates. As we encounter a growing co-morbid elderly population, the prevalence of this fracture-type will likely increase. Therefore, it is imperative clinicians continue to be attentive of atypical femoral fractures and treat them effectively.

• Bisphosphonates
• Atypical fracture
• Surgical fixation
• Atypical femoral fracture
• Osteoporosis

• RANKL clustering
• RANKL-binding peptide
• RANKL-reverse signaling
• bone formation
• bone resorption
• osteoprotegerin

Denosumab has been shown to increase bone mineral density (BMD) and reduce the fracture risk in patients with post-menopausal osteoporosis (PMO). Increase in BMD is linked with an increase in bone matrix mineralisation due to suppression of bone remodelling. However, denosumab anti-resorptive action also leads to an increase in fatigue microdamage, which may ultimately lead to an increased fracture risk. A novel mechanobiological model of bone remodelling was developed to investigate how these counter-acting mechanisms are affected both by exercise and long-term denosumab treatment. This model incorporates Frost's mechanostat feedback, a bone mineralisation algorithm and an evolution law for microdamage accumulation. Mechanical disuse and microdamage were assumed to stimulate RANKL production, which modulates activation frequency of basic multicellular units in bone remodelling. This mechanical feedback mechanism controls removal of excess bone mass and microdamage. Furthermore, a novel measure of bone local failure due to instantaneous overloading was developed. Numerical simulations indicate that trabecular bone volume fraction and bone matrix damage are determined by the respective bone turnover and homeostatic loading conditions. PMO patients treated with the currently WHO-approved dose of denosumab (60 mg administrated every 6 months) exhibit increased BMD, increased bone ash fraction and damage. In untreated patients, BMD will significantly decrease, as will ash fraction; while damage will increase. The model predicted that, depending on the time elapsed between the onset of PMO and the beginning of treatment, BMD slowly converges to the same steady-state value, while damage is low in patients treated soon after the onset of the disease and high in patients having PMO for a longer period. The simulations show that late treatment PMO patients have a significantly higher risk of local failure compared to patients that are treated soon after the onset of the disease. Furthermore, overloading resulted in an increase of BMD, but also in a faster increase of damage, which may consequently promote the risk of fracture, specially in late treatment scenarios. In case of mechanical disuse, the model predicted reduced BMD gains due to denosumab, while no significant change in damage occurred, thus leading to an increased risk of local failure compared to habitual loading.

• PK-PD modelling
• bone mineral density
• bone mineralisation
• bone turnover
• damage
• denosumab
• post-menopausal osteoporosis
• risk of failure

In a randomized controlled trial, we compared the bone mineral densities (BMDs) and blood markers of bone turnover during short-term treatment of osteoporotic women with bisphosphonate alendronate or bazedoxifene, a selective estrogen receptor modulator.

Ten and eleven patients were randomized to the alendronate and bazedoxifene groups, respectively. BMDs were measured before and after 6 months of treatment. Blood tests were used to measure the levels of osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), vitamin D3, and parathyroid hormone pretreatment and after 3 and 6 months of treatment. The variables were compared statistically.

The alendronate group showed decreases in blood levels of both OC and CTX during the study period (P<0.001 and P=0.002, respectively), while the bazedoxifene group had a decrease only in OC levels (P=0.012). After 6 months of treatment, BMDs significantly increased in the alendronate group at multiple bone sites, including the L1–4 lumbar vertebrae, femur trochanter, and total femur. However, there was no significant increase in BMD in the bazedoxifene group. BMDs were not significantly different between the 2 groups.

Patients treated with alendronate showed more rapid suppression of markers of bone turnover and higher BMD than those treated with bazedoxifene during a short-term regime. Considering the effects and complications of each medication, the relationship between bone turnover rate and bone quality will need to be investigated in future studies.

• Alendronate
• Bone density
• Bone resorption
• Osteogenesis
• Selective estrogen receptor modulators

Paget’s disease of bone (PDB) is a progressive bone disorder characterized by increased osteoclast-mediated bone resorption and abnormal bone formation. Incomplete atypical femoral fracture, appearing radiographically as a stress fracture at the lateral aspect of the femur, is an uncommon low-trauma fracture frequently seen in association with long-term bisphosphonate therapy. We describe the case of a 61-year-old female patient with PDB who developed a stress fracture at the lateral femoral cortex after 5 doses of intravenous bisphosphonate. The conservative treatment plan included discontinuation of bisphosphonate, a continuation of calcium and vitamin D supplementation, and limited weight-bearing for 3 months. The patient’s pain level gradually improved after switching to the new treatment plan. At the latest follow-up, approximately 5 years after the initiation of conservative treatment, the patient remained pain-free, and her PDB was well-controlled. However, the fracture line was still visible on the most recent radiograph. Although it remains unclear whether a stress fracture at the lateral femoral cortex occurred due to bisphosphonate therapy or PDB, this case highlights the importance of careful evaluation of any lesion that appears in PDB patients receiving bisphosphonate therapy.

• Femur
• Fracture healing
• Fractures, stress
• Osteitis deformans
• Paget’s disease of bone

• Atypical femoral fracture
• Bisphosphonates
• Complications
• Treatment

• Aging
• Bone
• Inflammation
• Osteoporosis
• Polyunsaturated fat
• Saturated fat

• Aged
• Aging
• Diet
• Dietary Fats
• Fatty Acids, Omega-3/therapeutic use
• Fatty Acids, Unsaturated
• Female
• Humans
• Male
• Obesity

• R01 DC013318 NIDCD NIH HHS

• acetylcholinesterase
• bone degeneration
• bone development
• bone homeostasis
• non-enzymatic
• osteoporosis

• Bone fragility
• Denosumab
• Drug holidays
• PK–PD modelling
• Postmenopausal osteoporosis
• RANK–RANKL–OPG pathway

Osteoblasts derived from mouse skulls have increased osteoclastogenic potential compared to long bone osteoblasts when stimulated with 1,25(OH)₂ vitamin D₃ (vitD₃). This indicates that bone cells from specific sites can react differently to biochemical signals, e.g., during inflammation or as emitted by bioactive bone tissue-engineering constructs. Given the high turn-over of alveolar bone, we hypothesized that human alveolar bone-derived osteoblasts have an increased osteogenic and osteoclastogenic potential compared to the osteoblasts derived from long bone. The osteogenic and osteoclastogenic capacity of alveolar bone cells and long bone cells were assessed in the presence and absence of osteotropic agent vitD₃. Both cell types were studied in osteogenesis experiments, using an osteogenic medium, and in osteoclastogenesis experiments by co-culturing osteoblasts with peripheral blood mononuclear cells (PBMCs). Both osteogenic and osteoclastic markers were measured. At day 0, long bones seem to have a more late-osteoblastic/preosteocyte-like phenotype compared to the alveolar bone cells as shown by slower proliferation, the higher expression of the matrix molecule Osteopontin (OPN) and the osteocyte-enriched cytoskeletal component Actin alpha 1 (ACTA1). This phenotype was maintained during the osteogenesis assays, where long bone-derived cells still expressed more OPN and ACTA1. Under co-culture conditions with PBMCs, long bone cells also had a higher Tumor necrose factor-alfa (TNF-α) expression and induced the formation of osteoclasts more than alveolar bone cells. Correspondingly, the expression of osteoclast genes dendritic cell specific transmembrane protein (DC-STAMP) and Receptor activator of nuclear factor kappa-Β ligand (RankL) was higher in long bone co-cultures. Together, our results indicate that long bone-derived osteoblasts are more active in bone-remodeling processes, especially in osteoclastogenesis, than alveolar bone-derived cells. This indicates that tissue-engineering solutions need to be specifically designed for the site of application, such as defects in long bones vs. the regeneration of alveolar bone after severe periodontitis.

• calcitriol
• cell differentiation
• jaw bone
• osteoblasts
• osteoclasts
• vitamin D3

• Alveolar Process/cytology
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Humans
• Osteoblasts/cytology
• Osteoclasts/cytology
• Osteogenesis
• Tibia/cytology

• animal experiments
• bone regeneration
• bone-implant interactions
• drug delivery
• guided tissue regeneration
• pharmacology

• NeuN
• Sox10
• bisphosphonates
• femoral nerve
• immunohistochemistry

• Administration, Oral
• Alendronate/administration & dosage
• Alendronate/adverse effects
• Alendronate/therapeutic use
• Animals
• Antigens, Nuclear/drug effects
• Antigens, Nuclear/metabolism
• Bone Density Conservation Agents/administration & dosage
• Bone Density Conservation Agents/adverse effects
• Bone Density Conservation Agents/therapeutic use
• Case-Control Studies
• Diphosphonates/administration & dosage
• Diphosphonates/adverse effects
• Diphosphonates/therapeutic use
• Female
• Femoral Nerve/drug effects
• Femoral Nerve/metabolism
• Femoral Nerve/physiopathology
• Femoral Nerve/ultrastructure
• Humans
• Immunohistochemistry/methods
• Models, Animal
• Myelin Sheath/drug effects
• Myelin Sheath/ultrastructure
• Nerve Tissue Proteins/drug effects
• Nerve Tissue Proteins/metabolism
• Osteoclasts/drug effects
• Osteoporosis, Postmenopausal/drug therapy
• Rats, Wistar
• SOXE Transcription Factors/drug effects
• SOXE Transcription Factors/metabolism

Osteoporotic patients being treated with bisphosphonates present an interesting dilemma when removing hardware such as dynamic hip screws “DHS”. In this paper, we describe the case of a 66-year-old osteoporotic patient who was placed on long term bisphosphonate therapy after sustaining an intertrochanteric hip fracture which was stabilized with a DHS. She presented with a subtrochantric fracture on the ipsilateral side. She was planned for DHS removal and intramedullary nailing. Removal of the dynamic hip screw proved to be difficult, likely due to possible cold welding of the DHS to the barrel of the side plate and sclerotic bone formation around the hardware secondary to the extended bisphosphonate use. The patient had an intra-operative femoral neck fracture while attempting the DHS removal. We had to convert to an unanticipated total hip replacement. Careful considerations should be taken when removing hardware from patients on long term bisphosphonate treatment.

• Bisphosphonate
• Case report
• Orthopedic surgery
• Subtrochanteric fracture

• bisphosphonate
• clodronate
• etidronate
• inflammation
• necrosis
• phosphate transporter

• Bisphosphonates
• Inorganic Pyrophosphate (PPi)
• cancer
• osteoclastogenesis
• osteoclasts
• vitamin D.

• differentiation
• osteogenesis
• signaling
• zebrafish

• Bone strength
• Ceramics
• Finite element analysis
• Hip fracture
• Osteoporosis
• Prophylactic injection

• Accidental Falls
• Aged
• Aged, 80 and over
• Biocompatible Materials
• Bone Substitutes/chemistry
• Calcium Sulfate/chemistry
• Calibration
• Durapatite/chemistry
• Female
• Femur/drug effects
• Femur/physiology
• Femur Neck
• Finite Element Analysis
• Flexural Strength
• Hip Fractures/physiopathology
• Humans
• Male
• Middle Aged
• Stress, Mechanical
• Tomography, X-Ray Computed

• Clinical Decision-Making
• Evidence-Based Medicine
• Humans
• Outcome Assessment, Health Care
• Precision Medicine/methods
• Randomized Controlled Trials as Topic
• Research Design
• Risk Assessment

• U01 NS086294 NINDS NIH HHS

• Bone
• Collagen
• Fragility
• Genetics
• Mineralization
• Osteogenesis imperfecta
• Proteoglycans

• Collagen Type I/genetics
• Collagen Type I/metabolism
• Extracellular Matrix/genetics
• Extracellular Matrix/metabolism
• Genetic Predisposition to Disease
• Humans
• Metabolic Networks and Pathways
• Molecular Targeted Therapy
• Mutation
• Osteogenesis Imperfecta/drug therapy
• Osteogenesis Imperfecta/genetics

• R01 AR060823 NIAMS NIH HHS

• EPIDEMIOLOGY
• GENERAL POPULATION STUDIES
• OSTEOPOROSIS
• STATISTICAL METHODS