Primary Osteoporosis Research Articles

Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians.

This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

Web Exclusive. Annals Video Summary - Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis.

Web Exclusive. Annals Video Summary - Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis.

Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

The prevalence of osteoporosis is increasing in the United States. To evaluate low bone mass and osteoporosis treatments to prevent fractures. Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare. American College of Physicians. (PROSPERO: CRD42021236220).

Summary for Patients: Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults

Summary for Patients: Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults

Osteoporoza

Osteoporosis is the most frequent metabolic bone disease. It is characterized by decreased bone strength and bone fractures and consequently decreased quality of life with increased morbidity and mortality. It affects the population of postmenopausal women and older people of both gender, but also patients with other primary diseases. Modern diagnostic procedures such as bone mineral density measurement, trabecular bone score (TBS) measurement, and fracture assessment risk score (FRAX) enable early diagnosis and treatment in high-risk patients. The complex etiology and pathophysiology of osteoporosis require secondary causes to be differentiated from primary osteoporosis before the most optimal treatment is initiated. The treatment should be personalized. Two methods of treatment are antiresorptive treatment aimed toward the inhibition of bone degradation and anabolic treatment with stimulation of new bone formation. Ideally, the prevention of fractures should be the treatment of choice, otherwise, prevention of new fractures and improvement of life is the therapeutic goal. Bisphosphonates are the first line antiresorptive treatment together with denosumab, a monoclonal human antibody against RANK ligand (receptor activator of nuclear factor kappa B). Teriparatide, an N-terminal parathormone fragment, is the dominant anabolic drug. Vitamin D deficiency is a widespread problem and contributes to bone mass decrement and increased risk for fractures. With further advancements in understanding the biology of bone tissue, new therapeutic agents are expected in the treatment of patients with osteoporosis.

Association between Dysbiosis in the Gut Microbiota of Primary Osteoporosis Patients and Bone Loss.

In recent decades, gut microbiome research has experienced significant growth, driven by technological advances that enable quantifying bacterial taxa with greater precision. Age, diet, and living environment have emerged as three key factors influencing gut microbes. Dysbiosis, resulting from alterations in these factors, may lead to changes in bacterial metabolites that regulate pro- and anti-inflammatory processes and consequently impact bone health. Restoration of a healthy microbiome signature could mitigate inflammation and potentially reduce bone loss associated with osteoporosis or experienced by astronauts during spaceflight. However, current research is hindered by contradictory findings, insufficient sample sizes, and inconsistency in experimental conditions and controls. Despite progress in sequencing technology, defining a healthy gut microbiome across global populations remains elusive. Challenges persist in identifying accurate gut bacterial metabolics, specific taxa, and their effects on host physiology. We suggest greater attention be directed towards this issue in Western countries as the cost of treating osteoporosis in the United States reaches billions of dollars annually, with expenses projected to continue rising.

Lessons learned from long-term side effects after zoledronic acid infusion following denosumab treatment: a case report and review of the literature

BackgroundZoledronic acid is an intravenous, highly potent aminobisphosphonate for use in patients with primary or secondary osteoporosis. Zoledronic acid-induced prolonged side-effects are well known and quite common. However, severe side-effects can be a threat to life. We report a case of severe side-effects induced by zoledronic acid infusion, and its positive effect on long-term back pain.Case presentationIn 2012, a 62-year-old white native Finnish woman was operated on for an estrogen and progesterone receptor-positive breast cancer. After radiotherapy, an aromatase inhibitor (letrozole) was started. Nine months after the operation, the patient suffered a low-energy compression fracture of Th XII. She received denosumab to prevent fragility fractures and to improve bone mineral density. Letrozole was discontinued after 5.5 years, and the last denosumab injection was given after 7 years. Six months later, at the age of 71 years, the patient received a single intravenous zoledronic acid infusion. Suddenly, at 10 hours from the infusion, she complained of severe trismus, muscle twitching, spasms, and tingling, matching hypocalcemia and several other symptoms. Her serum 25-hydroxyvitamin D concentration was high (163 nmol/L), the concentration of serum calcium and calcium-ion was normal (2.32 mmol/L and 1.23 mmol/L, respectively). However, the neutrophil to lymphocyte ratio (NLR) was low (1.6). A complete recovery took 2 months. Zoledronic acid infusion also had a positive effect: for many years, the patient had suffered low back pain and strain, which came to an end after this single infusion.ConclusionIt is important that the potential patients receive sufficient information about the possibility of side-effects following the administration of intravenous zoledronic acid. To ensure that a zoledronic acid infusion is given as safely as possible, the safety information should include that the patient should not be left without monitoring for a minimum 24 hours after the infusion. Being alone and experiencing serious side-effects may lead to acute cardiac problems. Furthermore, the chronic low back pain and strain that our patient suffered for many years has clearly reduced for 16 months after infusion, so far. We conclude that this is a positive effect of zoledronic acid.

Identification of key variants correlated with susceptibility of primary osteoporosis in the Chinese Han group.

Primary osteoporosis is a systemic skeletal disease characterized by reduced bone mass and vulnerability to fractures. The genetics of osteoporosis in the Chinese population remain unclear, which hinders the prevention and treatment of osteoporosis in China. This study aimed to explore the susceptibility genes and the roles played by their variants in osteoporosis. Blood samples were collected from 45 osteoporosis patients and 30 healthy individuals, and genome-wide association study was performed on array data. The expression levels of the candidate gene in different genotypes were further determined by using quantitative real-time PCR. Moreover, the differentiation capacity of bone marrow mesenchymal stem cells under different genotypes from osteoporosis patients was investigated. The most significant variant rs1891632 located in the upstream (918bp) region of CRB2, which could down-regulate the expression levels of CRB2 in genotype-tissue expression database and played an essential role in the regulation of osteoblastic and osteoclastic differentiation during skeletal development. Another significant variant rs1061657 located within the 3'UTR region of TBX3 gene. We found that the mRNA levels of TBX3 decreased in the bMSCs of old osteoporosis patients. Interestingly, osteoblast differentiation capacity and TBX3 mRNA levels were similar between the young healthy individuals carrying derived and ancestral allele of rs1061657, whereas the differentiation capacity and TBX3 mRNA levels dramatically declined in elderly patients with osteoporosis. The variant rs1061657 might affect the osteogenesis of bMSCs in an age-dependent manner and that TBX3 may be a key susceptibility gene for primary osteoporosis. In conclusion, CRB2 and TBX3 may influence the development of osteoporosis; additionally, rs1891632 and rs1061657, as the key variants first reported to be associated with primary osteoporosis, may potentially contribute to predicting the risk of osteoporosis (especially for older individuals) and may serve as therapeutic targets.

Can Polymorphisms in NLRP3 Inflammasome Complex Be Associated with Postmenopausal Osteoporosis Severity?

We genotyped 196 postmenopausal OP patients and 103 healthy controls using SNV-specific Taqman® probes. Data and statistical analyses were performed using the SNPstats and GraphPad Prism 8 software. We showed an association between NLRP3 rs35829419 CA genotype and lower bone mineral density (BMD) mean at the lumbar spine (p = 0.001); we also observed an association between IL-1β rs16944 AA genotype and higher BMD mean at the total hip (p = 0.009). The IL-1β rs16944 GG was associated with lower alkaline phosphatase levels (ALP) (p = 0.009), and the IL-18 rs1946519 AA was associated with lower vitamin D levels (p = 0.018). Additionally, OP patients presented deficient vitamin D and parathyroid hormone (PTH). The NLRP3 inflammasome complex SNVs were associated with OP severity, possibly indicating these genes' participation in bone metabolism and its dysregulation.

Risk of primary osteoporosis score (RPOPs): an algorithm model for primary osteoporosis risk assessment in grass-roots hospital

BackgroundThis study aimed to develop and validate a lasso regression algorithm model which was established by correlation factors of bone mineral density (BMD) and could be accurately predicted a high-risk population of primary osteoporosis (POP). It provides a rapid, economical and acceptable early screening method for osteoporosis in grass-roots hospitals.MethodsWe collected 120 subjects from primary osteoporosis screening population in Zhejiang Quhua Hospital between May 2021 and November 2021 who were divided into three groups (normal, osteopenia and osteoporosis) according to the BMD T-score. The levels of three micro-RNAs in the plasma of these people were detected and assessed by qRT-PCR. At the same time, the levels of β-CTX and t-P1NP in serum of the three groups were determined. Based on the cluster random sampling method, 84 subjects (84/120, 70%) were selected as the training set and the rest were the test set. Lasso regression was used to screen characteristic variables and establish an algorithm model to evaluate the population at high risk of POP which was evaluated and tested in an independent test cohort. The feature variable screening process was used 10-fold cross validation to find the optimal lambda.ResultsThe osteoporosis risk score was established in the training set: Risk of primary osteoporosis score (RPOPs) = -0.1497785 + 2.52Age − 0.19miR21 + 0.35miR182 + 0.17β-CTx. The sensitivity, precision and accuracy of RPOPs in an independent test cohort were 79.17%, 82.61% and 75%, respectively. The AUC in the test set was 0.80. Some risk factors have a significant impact on the abnormal bone mass of the subjects. These risk factors were female (p = 0.00013), older than 55 (p < 2.2e-16) and BMI < 24 (p = 0.0091) who should pay more attention to their bone health.ConclusionIn this study, we successfully constructed and validated an early screening model of osteoporosis that is able to recognize people at high risk for developing osteoporosis and remind them to take preventive measures. But it is necessary to conduct further external and prospective validation research in large sample size for RPOPs prediction models.

Network Meta-analysis of Oral Chinese Patent Medicine in Treatment of Primary Osteoporosis

The efficacy of oral proprietary Chinese medicine in the prevention and treatment of primary osteoporosis was systematically evaluated through a network meta-analysis. The computer retrieved the four major Chinese databases of CNKI, VIP, Wang Fang, CBM in China and abroad, as well as the three English databases and Web of Science of Medline, EMbase and Cochrane Library. The search cycle was designed as the database was established until February 15, 2022, and screened randomized controlled trials of export taking proprietary Chinese medicine combined with conventional western medicine for the prevention and treatment of primary osteoporosis according to the system evaluation pre-formulated exclusion criteria. Literature screening and data extraction are completed by at least 2 clinical investigators alone. Bias assessment and mapping of included studies using the Revman software, using the Cochrane Bias Risk Assessment tool, using Stata 16. 0 Software for data acquisition and analysis. In the end, 19 RCTS were included, involving 8 kinds of oral proprietary Chinese medicines (You Gui Pills, Jin Tiange Capsules, Gu Shu Kang Granules, Qiang Bone Capsules, Gu Songbao Granules, Xianling Gu Bao Capsules, Hu Gu Capsules, Zuo Gui Pills). The results of the network meta-study are as follows: (1) in terms of improving clinical efficiency, conventional western medicine combined with Hu Gu Capsules has the best effect; (2) in terms of improving bone density, conventional western medicine combined with Xianling Gu Bao has the best effect. This network meta-analysis provides evidence for the efficacy of the above eight proprietary Chinese medicines in the treatment of patients with POP.

Unveiling the transcriptomic landscape and the potential antagonist feedback mechanisms of TGF-β superfamily signaling module in bone and osteoporosis

BackgroundTGF-β superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have not yet been well characterized.MethodsTranscriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-β superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction.ResultsWe identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-β superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-β superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-β-mediated SMAD3 signaling and the genes encoding TGF-β superfamily antagonists served as significant features to osteoporosis.ConclusionOur data for the first time unveiled the transcription landscape of all the genes that make up TGF-β superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis.3vrgH_v5FiqyUZTyTihmKDVideo

Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature.

Irisin is a hormone-like myokine produced by the skeletal muscle in response to exercise. Upon its release into the circulation, it is involved in the browning process and thermogenesis, but recent evidence indicates that this myokine could also regulate the functions of osteoblasts, osteoclasts, and osteocytes. Most human studies have reported that serum irisin levels decrease with age and in conditions involving bone diseases, including both primary and secondary osteoporosis. However, it should be emphasized that recent findings have called into question the importance of circulating irisin, as well as the validity and reproducibility of current methods of irisin measurement. In this review, we summarize data pertaining to the role of irisin in the bone homeostasis of healthy children and adults, as well as in the context of primary and secondary osteoporosis. Additional research is required to address methodological issues, and functional studies are required to clarify whether muscle and bone damage per se affect circulating levels of irisin or whether the modulation of this myokine is caused by the inherent mechanisms of underlying diseases, such as genetic or inflammatory causes. These investigations would shed further light on the effects of irisin on bone homeostasis and bone disease.

Zoledronic acid for osteoporosis and associated low-energy fractures

Zoledronic acid is a third-generation amino-containing BF that has been used to treat patients with osteoporosis for more than 15 years. Over the years, numerous experimental and clinical studies have proven the high efficacy of the drug in osteoporosis, both in women of various age groups, and in men, with primary and secondary osteoporosis, in patients with varying degrees of bone loss and risk of fractures. Intravenous infusions of zoledronic acid have been shown to result in a rapid gain of bone mass, a significant reduction in the risk of low-energy fractures of the vertebrae (spine), proximal femoral and nonvertebral fractures on the whole. However, in recent years, the use of the drug has significantly decreased, which is associated both with the lack of awareness of primary care physicians about the possibilities of this drug, and the fear of such complications of its use as atypical fractures and osteonecrosis of the jaw bones. The presented review aims to increase the knowledge of physicians regarding the mechanism of action of zoledronic acid, the regimens for prescribing the drug in various forms of osteoporosis and fractures against its background. The given clinical example shows the ability of zoledronic acid (osteostatics) to increase the mass of not only cancellous, but also the cortical bone of the proximal femur, which increases the role of zoledronic acid in the prevention of recurrent fractures. On top of that, the prolonged effect of the drug allows, when the desired therapeutic effect is achieved, to reduce the frequency of prescribing according to the ‘drug holiday’ principal, decreasing economic expenditures and medical and social burden.

Osteoporosis related to WNT1 variants: a not infrequent cause of osteoporosis.

Recent studies have shown that homozygous WNT1 gene mutations may be related to severe osteoporosis resembling osteogenesis imperfecta (OI). Conversely, heterozygous WNT1 mutations are linked to a milder phenotype of early-onset osteoporosis. Treatment with bisphosphonates is reported to be unsatisfactory. Our aim was to analyze the presence and prevalence of WNT1 mutations and the main associated clinical characteristics in subjects with primary early-onset osteoporosis. A cohort comprising 56 subjects (aged 19-60years) with severe, early-onset osteoporosis was screened by massive parallel sequencing with a 23-gene panel. The gene panel included 19 genes known to cause OI (including the WNT1 gene), three genes related to osteoporosis, and the gene related to hypophosphatasia (ALPL). We identified five patients (3 men) with heterozygous WNT1 variants. All presented severe osteoporosis with early fracture onset and a family history of fragility fractures. None presented a characteristic phenotype of OI or skeletal deformities. One patient was previously treated with bisphosphonates, presenting inadequate response to treatment and two developed pseudoarthrosis after upper arm fractures. All subjects were diagnosed in adulthood. Nearly 1/10 adult subjects with severe idiopathic osteoporosis may present pathogenic WNT1 mutations. Clinical characteristics commonly include a family history of osteoporosis, onset in early adulthood, marked decrease in bone mass, and prevalent fractures, particularly vertebral. WNT1 should be genetically screened in these subjects as the phenotype is often variable and the therapeutic approach may differ. The role of WNT1 mutations in the development of pseudoarthrosis should also be elucidated.

Insufficiency fracture of the supra-acetabulum that required differentiation from a pathological fracture secondary to a malignant bone tumor: a case report

BackgroundThe supra-acetabulum is a common site for malignant bone tumors, which can be difficult to differentiate from insufficiency fractures. We report a rare case of a stress fracture of the supra-acetabulum that required differentiation from a malignant bone tumor.Case presentationA 74-year-old Japanese man presented to the hospital because of right hip joint pain. X-rays showed no obvious abnormalities. Magnetic resonance imaging showed an abnormality in the right supra-acetabulum, and he was referred to our department. A linear, low-signal region and its surrounding equal signal region were observed at the same site in the T1-weighted image, and a linear low-signal region and high signal region were observed in the surrounding area in the T2-weighted image. On the contrast-enhanced magnetic resonance imaging, the lesion was still unclear and the whole area was gradually enhanced. A computed tomography-guided needle biopsy was performed, but no tumor cells were observed, therefore the lesion was presumed to be a fracture healing. The bone density was 66% for the lumbar spine (young adult mean, L2–4), and blood biochemistry showed an increase in alkaline phosphatase and total type I procollagen N-terminal propeptide.ConclusionThis case was diagnosed as an insufficiency fracture of the supra-acetabulum in a male patient with primary osteoporosis by biopsy specimen. Initially, a pathological fracture associated with a malignant lesion was considered. On magnetic resonance imaging, the boundary around the fracture line was unclear and a signal change that was gradually enhanced by gadolinium was observed. This is likely to be bone marrow edema associated with the stress fracture, and we believe this to be a useful finding that may help in differentiating a stress fracture from a pathological fracture secondary to a malignant lesion.

Prevalence of Vertebral Compression Fracture Among Rheumatoid Arthritis Patients in Sulaymaniyah

Background: The risk of fractured vertebral increases in patients with rheumatoid arthritis as they are more likely to suffer from osteopenia, and osteoporosis. Objectives: This study aimed to investigating the rate and risk factors of vertebral fractures in patients with rheumatoid arthritis. Methods: We recruited 201 patients aged between 30 and 70 who attended the rheumatology department at Shahid Hemn Teaching Hospital in Sulaymaniyah, between January and September 2022. Medical records were reviewed for disease and treatment characteristics while also clinically evaluated by a rheumatologist. Spinal radiographs were assessed by two experienced radiologists blinded to patients’ clinical diagnosis and status. Compression fractures were classified by using the Genant semiquantitative method, and the type of fracture was classified as wedged fracture, biconcave fracture, or crushed fracture. Results: Of the 201 included participants, 151 were female, and 50 were male. The BMI of women was higher than men by nearly four points (P&lt;0.001). Most women were also illiterate (68/151, 45.0%) and unemployed (139/151, 92.1%). Hypertension (28.4%) and diabetes mellitus (14.4%) were the most reported comorbidities. Women were more likely to have higher DAS28 scores while men had more vertebral fractures (P=0.003). The probability of fractures increased with age, male sex, and illiteracy compared to primary school, osteopenia, and osteoporosis through simple and multiple logistic regression models. Conclusion: With at least one fracture affects females and males at a rate of 27.8% and 52.0%, respectively. Also reported that age, male sex, illiteracy, osteopenia, and osteoporosis significantly increase the risk of fractures.

Identifying vertebral fractures in the Japanese population using the trabecular bone score: a cross-sectional study

BackgroundThe trabecular bone score (TBS) is reported to be an independent predictor of fracture risk in patients with primary or secondary osteoporosis. However, there have been few reports on its use in the Japanese population. This study aimed to investigate the risk factors for vertebral fracture in the Japanese population and to evaluate the usefulness of TBS.MethodsThis cross-sectional study involved 279 patients aged 60–90 years in whom bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). TBS was calculated based on the DXA scans. The presence or absence of vertebral fractures was assessed from T11 to L5. The patients were divided into those with vertebral fractures (VF group, n = 104) and those without vertebral fractures (non-VF group, n = 175).ResultsOf the 104 patients in the VF group, 75 had 1 vertebral fracture and 29 had 2 or more fractures. The mean TBS was 1.28 in the VF group and 1.35 in the non-VF group (p < 0.001). The mean BMD values at the lumbar spine and femoral neck were lower in the VF group (p < 0.001). The areas under the receiver-operating characteristic curve for incidence of vertebral fractures were 0.700, 0.737, and 0.689 for TBS, lumbar spine BMD, and femoral neck BMD, respectively. Multiple logistic regression analysis identified lumbar spine BMD, TBS, and female sex as significant risk factors for vertebral fractures. The proportion of patients in the group with osteoporosis or osteopenia who had vertebral fractures was higher in those with a low TBS (≤ 1.23) than in those with a non-low TBS (> 1.23).ConclusionTBS was a significant indicator of vertebral fractures in the Japanese population and might contribute to identifying patients with vertebral fractures, particularly those with osteopenia who need pharmacologic therapy.

Risk factors associated with prevalent vertebral fractures in Duchenne muscular dystrophy.

Fragility fractures are frequent in DMD. The purpose of this study was to identify clinical factors associated with prevalent vertebral fractures (VF) in boys, teens/young adults with Duchenne muscular dystrophy (DMD). This was a cross-sectional study of males aged 4-25years with DMD. VF were evaluated using the modified Genant semi-quantitative method on T4-L4 lateral spine radiographs. Areal bone mineral density (aBMD) was measured at the lumbar spine (LS) and used to estimate volumetric BMD (vBMD). Clinical factors were analyzed for their association with the Spinal Deformity Index (SDI, the sum of the Genant grades). Sixty participants were enrolled (mean age 11.5years, range 5.4-19.5). Nineteen participants (32%) had a total of 67 VF; 23/67 VF (34%) were moderate or severe. Participants with VF were shorter (mean height Z-score ± standard deviation: - 3.1 ± 1.4 vs. - 1.8 ± 1.4, p = 0.001), had longer glucocorticoid exposure (mean duration 6.0 ± 3.3 vs. 3.9 ± 3.3years, p = 0.027), greater bone age (BA) delay (mean BA to chronological age difference - 3.2 ± 3.4 vs. - 1.3 ± 1.2years, p = 0.035), and lower LSaBMD Z-scores (mean - 3.0 ± 1.0 vs. - 2.2 ± 1.2, p = 0.023). There was no difference in LSvBMD Z-scores. Multivariable Poisson regression showed that every 0.1mg/kg/day increment in average glucocorticoid daily dose was associated with a 1.4-fold SDI increase (95% confidence interval: 1.1-1.7, p = 0.013). Greater BA delay (p < 0.001), higher weight Z-score (p = 0.004), decreased height Z-score (p = 0.025), and lower LSvBMD Z-score (p = 0.025) were also associated with SDI increase. Readily measurable clinical variables were associated with prevalent VF in males with glucocorticoid-treated DMD. These variables may be useful to identify candidates for primary osteoporosis prevention after glucocorticoid initiation.

Jump-landings that supersede bone health threshold requirements for premenopausal women

Osteoporosis is a disease characterized by a reduction in the density and quality of bone leading to a weakness of the skeleton and associated increased risk of fracture [1]. The most common type of osteoporosis is termed primary osteoporosis and includes both postmenopausal and age-related osteoporosis, which involves the structural deterioration of bone and increased porosity leading to increased fragility [2] (Figure 1).