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The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA.This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, -1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ -2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism.In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58.Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

Published literature on physicians' preferences and sequential treatment patterns of osteoporosis therapy is scarce.A retrospective cohort study of patients who received bisphosphonates, denosumab, and/or raloxifene for at least 3 consecutive years or teriparatide for at least 18 months for osteoporosis. Data collection spanned 10 years, from October 2007 to September 2016, at a tertiary care center in the United States.In total, 12 885 patients were identified on the basis of receiving at least 1 treatment at any point in time; 1814 patients were randomly reviewed, and 274 patients met the inclusion criteria. The mean age was 68.8 ± 10.7 years, and women represented 90.9% of all the cases. Primary care physicians and rheumatologists constituted 65.7% and 22.6% of the prescribers, respectively. Before instituting a drug holiday, alendronate was the most common initial treatment (percentage, mean duration ± standard deviation in years: 69%, 5.4 ± 2.4 years) followed by ibandronate (9.5%, 4.9 ± 2.1 years) and raloxifene (9.1%, 5.2 ± 1.6 years). Denosumab was the most common second course of treatment, accounting for 29.3% of 82 patients who were subsequently prescribed another therapy, followed by alendronate (24.4%) and zoledronate (20.7%). Among patients who were placed on a drug holiday and eventually restarted on osteoporosis therapy, denosumab was the most common treatment instituted (n = 21), accounting for 40% of the total patients, followed by alendronate (32%) and zoledronate (16%). There was a progressive decline in osteoporosis therapy over the duration of the study.Alendronate was the most common initial therapy. Denosumab was the most common second course of treatment prescribed.

Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings.We evaluated the effects of prunes (50 g or 100 g/d) on bone mineral density (BMD) in postmenopausal women during a 12-mo dietary intervention. Secondary outcomes include effects on bone biomarkers.The single-center, parallel-arm 12-mo randomized controlled trial tested the effects of 50 g and 100 g prunes compared with a control group on BMD (every 6 mo) and bone biomarkers in postmenopausal women.In total, 235 women (age 62.1 ± 5.0 y) were randomly allocated into control (n = 78), 50-g prune (n = 79), or 100-g prune (n = 78) groups. Compliance was 90.2 ± 1.8% and 87.1 ± 2.1% in the 50-g and 100-g prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100-g prune group (compared with other groups: 10%, control; 15%, 50 g prune; P 0.001). A group × time interaction for total hip BMD was observed in control compared with 50-g prune groups (P 0.05) but not in control compared with 100-g prune groups (P 0.05). Total hip BMD decreased -1.1 ± 0.2% in the control group at 12 mo, whereas the 50-g prune group preserved BMD (-0.3 ± 0.2%) at 12 mo (P 0.05). Although hip fracture risk (FRAX) worsened in the control group at 6 mo compared with baseline (10.3 ± 0.5% compared with 9.8 ± 0.5%, P 0.05), FRAX score was maintained in the pooled (50 g + 100 g) prune groups.A 50-g daily dose of prunes can prevent loss of total hip BMD in postmenopausal women after 6 mo, which persisted for 12 mo. Given that there was high compliance and retention at the 50-g dosage over 12 mo, we propose that the 50-g dose represents a valuable nonpharmacologic treatment strategy that can be used to preserve hip BMD in postmenopausal women and possibly reduce hip fracture risk. This trial was registered at clinicaltrials.gov as NCT02822378.

Vertebral fractures are associated with height loss, reduced quality of life, and increased mortality and are an important endpoint for osteoporosis trials. However, height loss is associated with quality of life and mortality independent of associations with fracture. We have used data from a recent 6-year trial of zoledronate in 2000 osteopenic women aged65 years to assess the impact of the semiquantitative and quantitative components of the definition of vertebral fracture on the outcome of that trial, to determine what factors impacted on height loss and to test whether height loss can be used as a surrogate for vertebral fracture incidence. In the trial protocol, an incident vertebral fracture was defined as a change in Genant grade plus both a 20% and 4 mm decrease in a vertebral height. The addition of the quantitative criteria reduced the number of fractures detected but did not change the size of the anti-fracture effect (odds ratios of 0.49 versus 0.45) nor the width of the confidence intervals for the odds ratios. Multivariate analysis of baseline predictors of height change showed that age accelerated height loss (p 0.0001) and zoledronate reduced it (p = 0.0001). Incident vertebral fracture increased height loss (p = 0.0005) but accounted for only 0.7% of the variance in height change, so fracture could not be reliably inferred from height loss. In women without incident vertebral fractures, height loss was still reduced by zoledronate (height change: zoledronate, -1.23; placebo -1.51 mm/yr, p 0.0001). This likely indicates that zoledronate prevents a subtle but widespread loss of vertebral body heights not detected by vertebral morphometry. Because height loss is associated with quality of life and mortality independent of associations with fracture, it is possible that zoledronate impacts on these endpoints via its effects on vertebral body integrity. © 2022 American Society for Bone and Mineral Research (ASBMR).

Context Recent meta-analyses of randomized controlled trials have raised concerns that denosumab might increase the risk of infection. However, data of denosumab on the risk of community-acquired pneumonia are sparse. Objective This work aimed to examine the risk of community-acquired pneumonia in individuals receiving denosumab compared to those receiving alendronate. Methods We conducted a propensity score-matched cohort study with a UK primary care database (IQVIA Medical Research Database). We examined the relation of denosumab to community-acquired pneumonia using a Cox proportional hazard model. The study participants were osteoporotic patients older than 45 years who were initiators of denosumab or alendronate from August 1, 2010, to September 17, 2020. The outcome measure was community-acquired pneumonia. Results Patients treated with denosumab (n = 933) were compared with those treated with alendronate (n = 4652). In the matched population, the mean (SD) age was 77 (11) years, 89% were women, and about half of the study population had a history of major osteoporotic fracture. Over 5 years of follow-up, the incidence of community-acquired pneumonia per 1000 person-years was 72.0 (95% CI, 60.1-85.7) in the denosumab group and 75.1 (95% CI, 69.4-81.2) in the alendronate group. The hazard of community-acquired pneumonia was similar between denosumab and alendronate users (hazard ratio [HR] 0.96; 95% CI, 0.79-1.16). The results remained consistent in a series of sensitivity analyses, with HR ranging from 0.82 (95% CI, 0.65-1.04) to 0.99 (95% CI, 0.81-1.21). Conclusion Denosumab does not significantly increase the susceptibility of community-acquired pneumonia and could possibly be safely used for the management of osteoporosis.

Periodontitis and osteoporosis are prevalent inflammation-associated skeletal disorders that pose significant public health challenges to our aging population. Both periodontitis and osteoporosis are bone disorders closely associated with inflammation and aging. There has been consistent intrigue on whether a systemic skeletal disease such as osteoporosis will amplify the alveolar bone loss in periodontitis. A survey of the literature published in the past 25 years indicates that systemic low bone mineral density (BMD) is associated with alveolar bone loss, while recent evidence also suggests a correlation between clinical attachment loss and other parameters of periodontitis. Inflammation and its influence on bone remodeling play critical roles in the pathogenesis of both osteoporosis and periodontitis and could serve as the central mechanistic link between these disorders. Enhanced cytokine production and elevated inflammatory response exacerbate osteoclastic bone resorption while inhibiting osteoblastic bone formation, resulting in a net bone loss. With aging, accumulation of oxidative stress and cellular senescence drive the progression of osteoporosis and exacerbation of periodontitis. Vitamin D deficiency and smoking are shared risk factors and may mediate the connection between osteoporosis and periodontitis, through increasing oxidative stress and impairing host response to inflammation. With the connection between systemic and localized bone loss in mind, routine dental exams and intraoral radiographs may serve as a low-cost screening tool for low systemic BMD and increased fracture risk. Conversely, patients with fracture risk beyond the intervention threshold are at greater risk for developing severe periodontitis and undergo tooth loss. Various Food and Drug Administration-approved therapies for osteoporosis have shown promising results for treating periodontitis. Understanding the molecular mechanisms underlying their connection sheds light on potential therapeutic strategies that may facilitate co-management of systemic and localized bone loss.

The goal of osteoporosis management is to prevent fractures. Several pharmacological agents are available to lower fracture risk, either by reducing bone resorption or by stimulating bone formation. Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50-70%, non-vertebral by 20-30%, and hip by ~40%). Bisphosphonates bind avidly to bone mineral and have an offset of effect measured in months to years. Long term, continuous use of oral bisphosphonates is usually interspersed with drug holidays of 1-2 years, to minimise the risk of atypical femoral fractures. Denosumab is a monoclonal antibody against RANKL that potently inhibits osteoclast development and activity. Denosumab is administered by subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of the bisphosphonates, but there is a pronounced loss of anti-resorptive effect from 7 months after the last injection, which can result in clusters of rebound vertebral fractures. Two classes of anabolic drugs are now available to stimulate bone formation. Teriparatide and abaloparatide both target the parathyroid hormone-1 receptor, and are given by daily subcutaneous injection for up to 2 years. Romosozumab is an anti-sclerostin monoclonal antibody that stimulates bone formation and inhibits resorption. Romosozumab is given as monthly subcutaneous injections for 1 year. Head-to-head studies suggest that anabolic agents have greater anti-fracture efficacy and produce larger increases in bone density than anti-resorptive drugs. The effects of anabolic agents are transient, so transition to anti-resorptive drugs is required. The optimal strategy for cycling anabolics, anti-resorptives, and off-treatment periods remains to be determined.

Abstract:: As a common systemically muscular-skeleton disorder of aging, osteoporosisis is characterized by the uninterrupted deconstruction in osseous microarchitecture. Osteoporosis can consequently lead to a significantly high risk of osteoporotic fractures, such as osteoporotic vertebral compressive fractures [OVCF] in the spine and osteoporotic femoral neck fractures in the hip joint, which can significantly increase the numbers of mortality and morbidity in elderly people, especially in postmenopausal women. In addition, vitamin K has been demonstrated to play a key role in inhibiting osteoporotic fractures among postmenopausal women, but its long-term benefits, potential harms, and side effects of the combination between vitamin K and other anti-osteoporosis medicines, such as bisphosphonates or teriparatide still remain to be extensively studied.Therefore, the present study aimed to systematically reviewed previously published literature on the role of vitamin K in the treatment of osteoporosis.We currently, via multiple query strategies, searched the relevant literature in Cochrane and PubMed from January 2010 to December 2019. Subsequently, we conducted the systematic review according to the standard guideline of Preferred Reporting Item for Systematic Reviews and Meta-Analyses [PRISMA]. Finally, ten relevant studies met our current criteria for inclusion; subsequently, we followed the PRISMA guideline, then systematically reviewed each study by categorizing the data sources and analytical approaches in each study, while setting up variables and defining each study's outcomes.

Objective: To evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. Materials and Methods: This prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. Results: With teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. Conclusion: P1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.

Osteoporosis is a critical problem during aging. Ultrasound signals backscattered from bone contain information associated with microstructures. This study proposed using entropy imaging to collect the information in bone microstructures as a possible solution for ultrasound bone tissue characterization. Bone phantoms with different pounds per cubic foot (PCF) were used for ultrasound scanning by using single-element transducers of 1 (nonfocused) and 3.5 MHz (nonfocused and focused). Clinical measurements were also performed on lumbar vertebrae (L3 spinal segment) in participants with different ages (n = 34) and postmenopausal women with low or moderate-to-high risk of osteoporosis (n = 50; identified using the Osteoporosis Self-Assessment Tool for Taiwan). The signals backscattered from the bone phantoms and subjects were acquired for ultrasound entropy imaging by using sliding window processing. The independent t-test, one-way analysis of variance, Spearman correlation coefficient rs, and the receiver operating characteristic (ROC) curve were used for statistical analysis. The results indicated that ultrasound entropy imaging revealed changes in bone microstructures. Using the 3.5-MHz focused ultrasound, small-window entropy imaging (side length: one pulse length of the transducer) was found to have high performance and sensitivity in detecting variation among the PCFs (rs = − 0.83; p p

As a selective estrogen receptor modulator (SERM), raloxifene is used in healthy postmenopausal women to prevent bone loss and reduce fractures. However, the benefit of raloxifene is uncertain in the treatment of osteoporosis among patients with end-stage renal disease (ESRD) or those who require maintenance dialysis. We assessed the safety and efficacy of raloxifene in this particular population. Studies were selected from PubMed, Springer, CNKI (Chinese National Knowledge Infrastructure) and Wanfang Database. Randomized controlled trials (RCTs) and prospective studies with control/placebo groups were included. Five studies were included with a total of 244 participants (121 patients in the raloxifene group and 123 patients in the placebo/control group). The median duration of treatment was 12 months. The incidence rate of side effects of raloxifene was 0/121 (0%). There was a significant improvement of lumbar spine bone mineral density (BMD) levels in the raloxifene group compared with the placebo group (MD: 33.88, 95% CI: 10.93, 56.84, p=0.004). There was no significant difference concerning the improvement of femoral neck BMD (MD: 8.42, 95% CI: –10.21, 27.04, p=0.38), intact parathyroid hormone (iPTH) (MD: –12.62, 95% CI: –35.36, 10.13, p=0.28), calcium (MD: -0.08, 95% CI: –0.61, 0.44, p=0.76), phosphorus (MD: 0.18, 95% CI: –0.12, 0.48, p=0.23) or bone alkaline phosphatase (BAP) (MD: –4.33, 95% CI: –14.44, 5.79, p=0.40). Raloxifene seems to be effective in improving the lumbar spine BMD in postmenopausal women with ESRD. More large RCTs are necessary to evaluate the long-term safety of raloxifene in uremic patients.

We registered 1336 incident-validated fractures in a prospective cohort of 3560 postmenopausal (60-85 years) Belgian women (mean follow-up of 9.1 years). The increase of fracture incidence with age varied widely depending on the fracture site and was significantly steeper for central than for peripheral fractures (e.g., not significant for the ankle).The epidemiology of fracture sites other than MOFs has been less studied. We examined the incidence of fractures according to their sites in a prospective cohort of postmenopausal Belgian women.Three thousand five hundred sixty postmenopausal women, aged 60-85 years old, were recruited from 2007 to 2013 and surveyed yearly (FRISBEE). The number of validated incident fractures was recorded and analyzed in relation to age and the fracture site.One thousand three hundred thirty-six fractures were recorded after a mean follow-up of 9.1 years. Seven hundred fifty-six fractures (57%) were MOFs and 580 (43%) non-MOFs, while 813 (61%) were central and 523 (39%) peripheral. The increase of fracture incidence with age differed between fracture sites and was steeper for central than for peripheral fractures. The ratio of MOFs to non-MOFs increased significantly with age, from 1.10 (95% CI: 0.83-1.45) for the 60-69 to 1.69 [1.42-2.01] for the 80-89-year subgroup (P = 0.017). This was also true for central versus peripheral fracture. We differentiated three groups of fracture incidence evolution with age: fractures with a mean increase/decade (compared to the 60-69 age group) of less than 1.5, 1.5-2.0, and 2.0-3.0. The lowest increase was seen for most peripheral fractures, whereas the greatest increase included hip, scapula, pelvis, ribs, and spine fractures.The increase of fracture incidence with age varied widely depending on the fracture site, and the ratio of MOFs to non-MOFs rose significantly with age. Some peripheral fractures, such as the ankle, did not increase significantly with age, suggesting that bone fragility does not play a major role in their occurrence.

Background As postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients. Methods Retrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis. Results Compared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P P P P P P Conclusion PMOP patients with advanced age, overweight, low bone mineral density, and comorbid chronic liver and kidney diseases are at greater risk of fractures and require early intervention to reduce fractures occurrence. Moreover, those who are elderly, overweight, and have low bone density should also be aware of the risk of re-fractures.

Osteoporosis is a chronic disease and affects an increasing number of people in the ageing population. Due to its ‛quiet' progress, it gradually impacts on the patient's daily functioning, resulting in reduction, then abandoning of existing forms of life activities and deterioration of mental state. The aim of the study was to analyze the levels of disease acceptance and satisfaction with life in women with postmenopausal osteoporosis depending on their body mass index.The study included a group of 198 women, 72.3 ± 8.59 years old, diagnosed with postmenopausal osteoporosis treated in two Osteoporosis Treatment Centers in the city of Lodz. The study used the Acceptance of Illness Scale (AIS), the Satisfaction with Life Scale (SWLS), the Visual Analogue Scale (VAS), and a self-made survey.The mean AIS score was 25.95 ± 10.20 points, which indicated a moderate level of acceptance and adjustment to the disease in the study group. The average level of satisfaction with life assessed on the SWLS was 19.37 ± 7.31 points and indicated moderate life satisfaction. The lowest acceptance of the disease (24.38 ± 11.3 points) was presented by underweight persons, while the lowest satisfaction with life (17.75 ± 7.50 points) was presented by overweight women. The subjects presented a mild level of pain according to the VAS scale (4.87 ± 2.39 points). The highest acceptance of the disease and satisfaction with life was presented by normal weight persons.The levels of disease acceptance and satisfaction with life in women with postmenopausal osteoporosis do not differ statistically significantly depending on body mass index. It was indicated that greater acceptance of the disease was accompanied by greater satisfaction with life in people with osteoporosis. Psychological aspects (AIS, SWLS) should be an important component of the assessment of therapy effectiveness in women undergoing a long-term treatment for postmenopausal osteoporosis.

Intravenous zoledronate reduces fracture risk (5 mg at 18-month intervals) and prevents bone loss (doses of 1 to 5 mg for 3 to >5 years), but the duration of action of a single 5 mg dose and the effects of lower doses beyond 5 years are unknown. We report the second open-label extension (years 5 to 10) of a 2-year randomized, multidose, placebo-controlled, double-blinded trial. A total of 116 older women who completed 5 years of participation either continued observation without further treatment (zoledronate 5 mg and placebo at baseline) or received repeat doses of 1 or 2.5 mg zoledronate (zoledronate 1 mg and zoledronate 2.5 mg at baseline, respectively). Outcomes were spine, hip, and total body bone mineral density (BMD) and serum markers of bone turnover. After a single 5 mg dose of zoledronate, mean BMD at the lumbar spine and total hip was maintained at or above baseline levels for 9 and 10 years, respectively. The mean level of the bone resorption marker β-C-terminal telopeptide of type I collagen (β-CTX) was at least 25% lower than that in the placebo group for 9 years. In women administered 5-yearly doses of 2.5 mg zoledronate, mean BMD at the total hip and lumbar spine was maintained at or above baseline levels for 9 and 10 years, respectively. Redosing with 1 or 2.5 mg zoledronate at 5 years reduced bone turnover markers for 3 to 4 years. BMD increased for 3 to 4 years after redosing with 1 mg zoledronate. In the group given 5-yearly 2.5 mg zoledronate, β-CTX was at least 20% lower than that in the placebo group for 10 years. Both a single baseline 5 mg dose of zoledronate and 5-yearly doses of 1 and 2.5 mg zoledronate prevented bone loss at hip and spine for 8 to 10 years in older postmenopausal women. Clinical trials to evaluate the effects on fracture risk of these very infrequent and lower doses of zoledronate are justified. © 2021 American Society for Bone and Mineral Research (ASBMR).

The 2020 American Association of Clinical Endocrinologists guidelines for assessing osteoporosis among postmenopausal women stratified postmenopausal women with osteoporosis to "high" and "very-high" fracture risk categories and recommended anabolic agents as initial therapy followed by an antiresorptive agent. Switching the order can blunt the effect of anabolic agents, and failing to follow with an antiresorptive can lead to loss of bone generated by the anabolic agent. It would be helpful to understand the real-world prescribing patterns of anabolic agents. Using the 2010-2015 Medicare 100% osteoporosis database, we assessed patient profiles, teriparatide prescribers, persistence of teriparatide therapy, and antiresorptive agent use after teriparatide discontinuation among elderly women who initiated teriparatide from 2011 to 2013. This study included 14,786 patients. In the year before teriparatide initiation, 30.0% of them had a fracture, 67.6% had a dual energy x-ray absorptiometry scan, 74.4% had a diagnosis of osteoporosis, and 47.9% used antiresorptive agents (non-naïve teriparatide users). Among those who had fractures, 49.4% initiated teriparatide within 3 months postfracture. Teriparatide was prescribed for 37% of users by primary care doctors, 19% by rheumatologists, 13% by endocrinologists, and 7.0% by orthopedists. Median time of teriparatide use was 7.2 months. After teriparatide discontinuation, 40.8% switched to antiresorptive agents (31.9% among naïve teriparatide users, 50.5% among non-naïve users). Among switchers, 42.5% switched within 60 days, 50.5% switched to denosumab, and 31.6% switched to oral bisphosphonates. This study of real-world prescribing data found that about half of teriparatide users switched from an antiresorptive agent, and less than half switched to antiresorptive agents after teriparatide discontinuation. Persistence of teriparatide use was suboptimal. In the management of postmenopausal osteoporosis, increasing the persistence of teriparatide use and improving the appropriate treatment sequence of anabolic and antiresorptive drugs are critical to maximizing gains in bone mass, providing the greatest protection against fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Background Osteoporosis (OP) is the most common type of systemic bone disease characterized by low bone mass and micro-structure deterioration of bone tissue, with a consequent increase in bone fragility and fracture risk. Nitric oxide (NO), produced by the enzyme endothelial nitric oxide synthase (eNOS) in endothelial cells, has considerable effects on bone cell function. The objective of this case-control study was to investigate the potential association between the eNOS gene Variable Number Tandem Repeat (VNTR) variant and susceptibility of OP, in a sample of Turkish postmenopausal female patients. Methods One hundred and fifty female patients and 100 age -matched healthy females enrolled in the present study. The eNOS gene VNTR variant was genotyped with a polymerase chain reaction (PCR) method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results The mean age of the patients was 60.32±8.65 years. It was found that the eNOS VNTR variant genotype and allele frequencies were not significantly different between the patient and control groups (p>0.05). Conclusion Genetic variants are important for our understanding of OP pathogenesis. Although we could not find a relationship between the eNOS VNTR variant and postmenopausal OP, it is important that this study is the first study investigating the relationship between the eNOS gene VNTR variant and OP in Turkish women.

The Asian and Latin America Fracture Observational Study (ALAFOS) is a prospective, observational, single-arm study conducted in 20 countries across Asia, Latin America and the Middle East. ALAFOS evaluated new clinical vertebral and non-vertebral fragility fractures in relation to time on teriparatide, in postmenopausal women with osteoporosis in real-life clinical practice. Clinical fragility fractures, back pain, and health-related quality of life (HRQoL) were recorded in 6-month intervals for ≤ 24 months during teriparatide treatment and up to 12-months post-treatment. Data were analysed with piecewise exponential regression with inverse probability weighting for time to event outcomes and mixed-model repeated measures for back pain and HRQoL. 3054 postmenopausal women started teriparatide and attended ≥ one follow-up visit (mean [SD] age 72.5 [10.4] years). The median (95% CI) time to treatment discontinuation was 22.0 months (21.2, 22.8). During the treatment period, 111 patients (3.6%) sustained 126 clinical fractures (2.98 fractures/100 patient-years). Rates of new clinical fragility fractures were significantly decreased during the > 6–12, > 12–18, and > 18–24-month periods, as compared with the first 6 months of treatment (hazard ratio [HR] 0.57; 95% CI 0.37, 0.88; p = 0.012; HR 0.35; 95% CI 0.19, 0.62; p p = 0.011; respectively). Patients also reported an improvement in back pain and HRQoL (p

Osteoporosis is one of the chronic and often neglected bone diseases in aging postmenopausal women that affect the quality of life. Studies on ovariectomized mice models indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. While Th17 cells promote osteoclastogenesis, Treg cells exhibit anti-osteoclastogenic activity. This exploratory study aimed to determine the difference in the frequency of these T-cell subtypes in pre-and postmenopausal women and to examine their association with BMD. In our study, the frequency of Treg cells, analyzed by flow cytometry, did not differ between pre-and postmenopausal women. However, plasma levels of IL-10 along with IL-10+CD4+T cells were higher in post- compared to premenopausal women. The frequency of Th17 cells was higher in postmenopausal women irrespective of their BMD, however, only postmenopausal women with low BMD had elevated IL-17 levels and their T-scores were associated with Th17 frequency. Collectively, the results suggest that estrogen insufficiency in postmenopausal women may lead to increased Th17 cell frequency and elevated IL-17 levels which are associated with low BMD. This study highlights, Th17 cells and IL-17 as key players in the pathogenesis of osteoporosis and they can be the potential targets for immunotherapy in the treatment of osteoporosis.

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 μg or placebo for 12 months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n = 149; placebo, n = 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T-score, -2.1). At 12 months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p 0.0001). The most common (≥5%) treatment-emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12 months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Prevention of fragility fractures is one of the public health priorities worldwide, whilst the incidence of osteoporotic vertebral compression fractures (OVCF) continues to rise and lacks the corresponding accurate prediction model. This study aimed to screen potential causes and risk factors for primary non-traumatic osteoporotic vertebral compression fractures (NTOVCF) in the elderly by characterizing a patient population with NTOVCF and comparing it with a population of osteoporotic patients.Between January 2013 and January 2022, 208 elderly patients with unequivocal evidence of bone fragility manifested as painful NTOVCF were enrolled, and compared with 220 patients with osteoporosis and no fractures. The demographic data, bone turnover markers, blood routine, serum biochemical values, and radiological findings were investigated. Differences between the fracture and non-fracture groups were analyzed, and variables significant in univariate analysis and correlation analysis were included in the logistic analysis to build the risk prediction model for osteoporotic vertebral fractures. Univariate analysis using student's t-tests for continuous variables or a chi-squared test for categorical variables was conducted to identify risk factors.No significant differences were revealed regarding age, gender, BMI, smoking, alcohol consumption, blood glucose, propeptide of type I procollagen (P1NP), and N-terminal middle segment osteocalcin (N-MID) (P 0.05). Parathyroid Hormone (PTH), 25(OH)D, serum albumin (ALB), hemoglobin (HB), bone mineral density (BMD), and cross-sectional area (CSA) of the paraspinal muscle in the fracture group were significantly lower than those in the control group; however, b-C-terminal telopeptide of type I collagen (β-CTX), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-prostatic acid phosphatase (NACP), and fatty degeneration ratio (FDR) were significantly higher than those in the control group (P 0.05). Logistic regression analysis showed that ALB, HB, CSA, and BMD were negatively correlated with NTOVCF, while β-CTX, HDL-C, NACP, and FDR were positively correlated with NTOVCF.Decreased physical activity, anemia, hypoproteinemia, imbalances in bone metabolism, abnormal lipid metabolism, and degenerative and decreased muscle mass, were all risk factors for OVCF in the elderly, spontaneous fractures may be the consequence of cumulative declines in multiple physiological systems over the lifespan. Based on this risk model, timely detection of patients with high OVCF risk and implementation of targeted preventive measures is expected to improve the effect of fracture prevention.

Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting mainly postmenopausal women and older adults. Osteoporosis is characterized by an imbalance between bone resorption and bone production. It is diagnosed through different methods such as bone densitometry and dual X-rays. The treatment of this pathology focuses on different aspects. On the one hand, pharmacological treatments are characterized by the use of anti-resorptive drugs, as well as emerging regenerative medicine treatments such as cell therapies and the use of bioactive hydrogels. On the other hand, non-pharmacological treatments are associated with lifestyle habits that should be incorporated, such as physical activity, diet and the cessation of harmful habits such as a high consumption of alcohol or smoking. This review seeks to provide an overview of the theoretical basis in relation to bone biology, the existing methods for diagnosis and the treatments of osteoporosis, including the development of new strategies.

Therapeutic regimens for osteoporosis are the key elements in the management of osteoporotic patients.The aim of the study was to present data on changes in osteoporosis therapy in women during a 10‑year follow‑up.We analyzed a population‑based sample recruited in the RAC‑OST‑POL study. At baseline, the cohort included 978 women, of whom 541 remained in the follow‑up. Mean (SD) age of the patients was 74.7 (6.6) years.The number of untreated women and those on alendronate decreased, while the number of patients receiving other forms of the antiresorptive therapy or calcium / vitamin D supplementation increased during the study. The percentage of untreated women in the rural areas and the urban areas was, respectively, 85% and 74.1% at baseline, and 74.3% and 63.3% at the end of the follow‑up. The percentage of untreated women decreased significantly, both in rural and urban cohorts. It was accompanied by a significant increase in calcium / vitamin D supplementation in both subgroups. Regarding the antiresorptive therapy, there was a significant increase in the frequency of its use only in the rural cohort. The use of therapeutic strategies was determined by the level of education. The frequency of calcium and / or vitamin D supplementation increased significantly in all education-related categories during the follow‑up.Changes in the therapy of postmenopausal women with osteoporosis, observed in a 10‑year follow‑up of the RAC‑OST‑POL study, indicated that the level of care did not improve in this group of patients.

Mini abstract: Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Summary: Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions. Introduction: The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723). Methods: Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model. Results: Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts. Conclusions: Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Purpose In osteoporosis, prior fracture is a strong predictor of subsequent fracture. This study aimed to assess the imminent risk of subsequent fracture following an initial fracture in osteoporosis patients in Germany, and to identify clinical and demographic characteristics that are independently associated with subsequent fracture risk. Methods In this retrospective, observational cohort study using German real-world claims data, male and female patients aged ≥ 50 years with osteoporosis who experienced an initial (“index”) hip/femur, vertebral, forearm/wrist/hand or shoulder/upper arm fracture between 2010 and 2014 were included. The incidence and timing of subsequent fractures during a 1-year follow-up period were analyzed. Independent risk factors for subsequent fracture were identified by multivariate regression analysis. Results A total of 18,354 patients (mean age: 77 years; standard deviation: 9.8) were included. Of these, 2918 (15.9%) suffered a subsequent fracture during the 1-year follow-up period. The incidence of subsequent fracture was higher following an index vertebral fracture (18.0%) than after an index forearm/wrist/hand fracture (14.1%) or index hip/femur fracture (12.1%). Subsequent 1-year fracture incidence was generally higher in older patients. Index fracture type, age, epilepsy/use of antiepileptics, and heart failure were all independently associated with subsequent fracture risk. Conclusion Osteoporosis patients in Germany are at imminent risk of subsequent fracture during the first year following an initial fracture. They should be targeted for immediate post-fracture treatment to reduce the risk of further fractures, especially in the presence of specific risk factors such as old age or index vertebral fracture.

Summary Osteoporosis, a chronic disease, requires long-term therapy. In Medicare-insured women, denosumab persistence was higher than oral bisphosphonate persistence over up to 3 years of follow-up. Longer-term persistence was higher among women who persisted in the first year of therapy. Introduction Osteoporosis, a chronic, progressive disease, requires long-term therapy; this study assessed long-term persistence with anti-resorptive therapies in postmenopausal women. Methods This retrospective cohort study used administrative claims for women with data in the 100% Medicare osteoporosis sample who initiated (index date) denosumab, oral/intravenous (IV) bisphosphonate, or raloxifene between 2011 and 2014 and who had ≥ 1 year (zoledronic acid: 14 months) of pre-initiation medical/pharmacy coverage (baseline). Persistence was assessed from index date through end of continuous coverage, post-index evidence of censoring events (e.g., incident cancer), death, or end of study (December 31, 2015). Results The study included 318,419 oral bisphosphonate users (78% alendronate), 145,056 denosumab users, 48,066 IV bisphosphonate users, and 31,400 raloxifene users; mean age ranged from 75.5 years (raloxifene) to 78.5 years (denosumab). In women with at least 36 months of follow-up (denosumab N = 25,107; oral bisphosphonates N = 79,710), more denosumab than oral bisphosphonate initiators were persistent at 1 year (73% vs. 39%), 2 years (50% vs. 25%), and 3 years (38% vs. 17%). Persistence decreased over time for all treatment groups, with denosumab users having the highest persistence in every follow-up time interval at or after 18 months. Women using denosumab, oral bisphosphonates, or raloxifene who persisted in a given year were more likely to remain persistent through the subsequent year. Conclusions Denosumab users persisted longer with therapy than women using other anti-resorptive medications, including oral bisphosphonates. Early persistence may predict long-term persistence. Overall persistence with osteoporosis medications is suboptimal and may impact fracture risk. Efforts to improve first year persistence are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05951-1.

BACKGROUND: New bone-directed therapies, including denosumab, abaloparatide, and romosozumab, emerged during the past decade, and recent trends in use of these therapies are unknown. OBJECTIVE: To examine temporal trends in bone-directed therapies. DESIGN: An open cohort study in a US commercial insurance database, January 2009 to March 2020. PARTICIPANTS/INTERVENTIONS: All-users of bone-directed therapies age >50 years, users with osteoporosis, users with malignancies, and patients with recent (within 180 days) fractures at key osteoporotic sites. MAIN MEASURES: The percentage of each cohort with prescription dispensing or medication administration claims for each bone-directed therapy during each quarter of the study period. KEY RESULTS: We analyzed 15.48 million prescription dispensings or medication administration claims from 1.46 million unique individuals (89% women, mean age 69 years). Among all users of bone-directed therapies, alendronate, and zoledronic acid use increased modestly (49 to 63% and 2 to 4%, respectively, during the study period). In contrast, denosumab use increased rapidly after approval in 2010, overtaking use of all other medications except alendronate by 2017 and reaching 16% of users by March 2020. Similar trends were seen in cohorts of osteoporosis, malignancy, and recent fractures. Importantly, use of any bone-directed therapy after fractures was low and declined from 15 to 8%. CONCLUSIONS: Rates of denosumab use outpaced growth of all other bone-directed therapies over the past decade. Treatment rates after osteoporotic fractures were low and declined over time, highlighting major failings in osteoporosis treatment in the US. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06938-8.

Denosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic effects or safety in postmenopausal osteoporosis. This retrospective observational registry study compared the efficacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a significant difference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also significantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were significantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was significantly increased at 6 months and then returned to baseline, while the bone resorption marker was significantly decreased at both time points. Adverse events were few and predominantly minor in both groups, with no remarkable difference in the incidence of new vertebral fractures. Romosozumab showed a higher potential for improving BMD than denosumab in this clinical study of postmenopausal osteoporosis patient treatment.

OBJECTIVE In this study the effect of the add-on effect of the tree pose (vrksasana), on the balance of patients with postmenopausal osteoporosis was investigated. DESIGN Thirty-two patients with postmenopausal osteoporosis were randomly assigned to conservative exercise group (EXE, 30-minutes/day 12-week) or tree pose added exercise group (EXE+YOGA, 30-minutes conventional exercise + 2-minutes tree pose/day 12-week) by Microsoft Excel randomization option. The balance of the patients were evaluated with berg balance scale, timed up&go test, single leg standing test, tandem walk test, tandem stance test, korebalance static&dynamic balance tests baseline, 6th week and at 3rd month of the exercise program. RESULTS There was no statistically significant difference on baseline data between groups. There was a statistically significant difference between the two groups in the 6th week measurement of single leg stance (p

The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis. Antibody-based Wnt agonists are able to phenocopy Wnt signaling in vivo resulting in increased bone density, repair, and strength. Here, the authors show that Wnt agonists can reverse bone loss associated with ovariectomy and build stronger bone when administered after fracture.

As a necessary trace element, iron is involved in many physiological processes. Clinical and basic studies have found that disturbances in iron metabolism, especially iron overload, might lead to bone loss and even be involved in postmenopausal osteoporosis. Hepcidin is a key regulator of iron homeostasis. However, the exact role of hepcidin in bone metabolism and the underlying mechanism remain unknown. In this study, we found that in postmenopausal osteoporosis cohort, the concentration of hepcidin in the serum was significantly reduced and positively correlated with bone mineral density. Ovariectomized (OVX) mice were then used to construct an osteoporosis model. Hepcidin overexpression in these mice significantly improved bone mass and rescued the phenotype of bone loss. Additionally, overexpression of hepcidin in OVX mice greatly reduced the number and differentiation of osteoclasts in vivo and in vitro. This study found that overexpression of hepcidin significantly inhibited ROS production, mitochondrial biogenesis, and PGC-1β expression. These data showed that hepcidin protected osteoporosis by reducing iron levels in bone tissue, and in conjunction with PGC-1β, reduced ROS production and the number of mitochondria, thus inhibiting osteoclast differentiation and bone absorption. Hepcidin could provide new targets for the clinical treatment of postmenopausal osteoporosis.

Human body height loss of 3–4 cm or more may be considered a simple indicator of increasing fracture risk, where the information is very similar to the results from fracture risk assessments by available online calculators, all of them based on a multiple variable approaches. The aim of the study was to assess the relationship between body height loss (HL) and fracture risk in postmenopausal women from the Gliwice Osteoporosis (GO) Study. The study sample included 1735 postmenopausal women, aged over 55 years and recruited at the Osteoporotic Outpatient Clinic. The mean age of the study participants was 68.15 ± 8.16 years. Fracture risk was established, using the fracture risk assessment tool (FRAX) (10-year probability of major and hip fractures), the Garvan calculator (any and hip fractures, 5 and 10 years) and the Polish (POL-RISK) algorithm, available at www. fracture - risk .pl (any fractures, 5 years). Bone densitometry at the femoral neck was performed, using a Prodigy device (Lunar, GE, USA). Body heights were measured before bone densitometry, using a wall stadiometer and compared with the maximum body heights, measured in early adulthood and reported by the study participants themselves. In 199 women, the body heights, measured during the study, did not change in comparison to their corresponding values in early adulthood, while being decreased in the other 1536 women. The mean height loss (HL) in the whole study group was 3.95 ± 3.24 cm. That HL correlated significantly with the calculated fracture risk (the r range from 0.13 to 0.39, p < 0.0001). In general, regarding the patients with fracture risk close to the recommended therapeutic thresholds, HL was around 3–4 cm, except of the values from the FRAX calculator for major fractures, where the commonly used therapeutic threshold (20%) was related to HL of approximately 6.5 cm. In subjects with HL between 3.5 and 4 cm (n = 208), the FRAX value for major fractures was 6.83 ± 3.74. Body height measurements, carried out to establish HL, provide an important information for clinical practice, where HL of 3–4 cm or more may be considered a simple indicator of increasing fracture risk.

Backgroud The purpose of this study was to investigate the characteristics of osteoporotic vertebral compression fractures (OVCFs) in Korean postmenopausal women and the association between OVCFs and clinical factors such as age, bone mineral density (BMD), and quality of life. Methods According to the population distribution in four regions in Korea, 1,281 postmenopausal female patients were recruited from nationwide orthopedic outpatient clinics. Radiologic, asymptomatic, and within 3 months of OVCF groups were analyzed based on age, fracture location, and prevalence according to BMD. In addition, BMD, T-score, body mass index, and European Quality of Life-5 Dimensions (EQ-5D) were investigated in the three groups, and the differences between groups were compared and analyzed. Results The prevalence of radiologic OVCFs at the T11-L1 was 3.7 times higher in the 70s group (44.0%) than in the 50s group (11.9%). Femur and total hip BMD were significantly lower in patients with thoracolumbar junction fractures than in patients with L2-5 fractures, whereas no difference was observed in lumbar spine BMD. Of the three OVCF groups, the within 3 months of OVCF group had the lowest lumbar spine T-score of -2.445. The asymptomatic OVCF group also showed significantly lower lumbar spine T-score than did the group without radiologic OVCFs (p < 0.001). The EQ-5D showed a significant decrease in the radiologic OVCF group (p < 0.001) and within 3 months of OVCF group (p < 0.001). Conclusions The prevalence of OVCFs in the thoracolumbar junction rapidly increases with old age and low BMD in Korean postmenopausal women. Femur and total hip BMD are more predictive of thoracolumbar junction fractures than lumbar spine BMD. Patients with radiologic OVCFs had a significantly lower quality of life than no OVCF group. Therefore, this study shows it is important to treat and prevent osteoporosis before an OVCF occurs.

Background The prevalence of osteoporosis is rising steadily as the aging population increases. Bone mineral density (BMD) assessment is a golden standard to establish the diagnosis of osteoporosis. However, the accessibility and radiation exposure limited its role in community screening. A more convenient approach for screening is suggested. Methods A total of 363 postmenopausal women over the age of 50 were included in this study and assessed with the body composition [including fat-free mass (FFM), fat mass (FM), and basal metabolic rate (BMR)] and BMD. Normal distributions and correlation coefficients among variables were calculated using the Shapiro-Wilk test and Pearson’s correlation analysis, respectively. A receiver operating characteristic (ROC) curve was plotted, and the area under ROC curves (AUC) was determined to obtain the optimal cutoff values of the body composition variables for osteoporosis prediction. Results The correlation coefficient of FFM, FM, FM ratio, and BMR with femur neck T-score was 0.373, 0.266, 0.165, and 0.369, respectively, while with spine T-score was 0.350, 0.251, 0.166, and 0.352, respectively (p < 0.01 for all). FFM, FM, and BMR showed an optimal cutoff value of 37.9 kg, 18.6 kg, and 1187.5 kcal, respectively, for detecting osteoporosis. Conclusions The present study provided a model to predict osteoporosis in postmenopausal women, and the optimal cutoff value of FFM, FM, and BMR could be calculated in the Asian population. Among these factors, BMR seemed a better predictor than others. The BMR could be a target for exercise intervention in postmenopausal women for maintaining or improving BMD. Trial registration ClinicalTrials.gov, NCT02936336. Retrospectively registered on13 October 2016.

Yuzhang Tao,1 Siying Tang,2 Xiao Huang,1 Hongwei Wang,1 Aiguo Zhou,1 Jian Zhang1 1Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jian ZhangDepartment of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaEmail zhangjian@hospital.cqmu.edu.cnBackground: Total knee arthroplasty (TKA) complications associated with low bone quality are challenging for orthopaedic surgeons to treat, but little is known about bone quality in Chinese postmenopausal women awaiting TKA. This study investigated the incidence of osteoporosis (OP) and explored the preoperative risk factors for OP in this population.Methods: We retrospectively reviewed the data of Chinese postmenopausal women who were indicated for TKA between May 2017 and June 2020. The bone mineral density (BMD) of the hip and lumbar spine and multiple preoperative parameters were collected and analyzed. Binary logistic regression analysis was performed to identify independent risk factors for OP in this population.Results: A total of 204 postmenopausal women with advanced knee OA were included in the study (age: 69.7± 8.5 years; body mass index [BMI]: 25.5± 4.0 kg/m2). The OP prevalence among all participants was 59.8%, and the patients aged 60– 80 years had a significantly lower BMD than did the age/ethnicity-adjusted population. An age ≥ 60 years, a BMI< 25, and the presence of a varus knee deformity were independent risk factors for preoperative OP in the postmenopausal women awaiting TKA.Conclusion: The prevalence of OP in Chinese postmenopausal women awaiting TKA is higher than that in the age/ethnicity-adjusted normal population. An age ≥ 60 years, a BMI< 25, and the presence of a varus knee deformity are independent risk factors that can be used to predict preoperative OP in this population.Keywords: osteoporosis, postmenopausal women, total knee arthroplasty, Chinese, bone mineral density

Osteoporosis or decreased bone mineral density (BMD) is the most important risk factor for fractures, especially in older postmenopausal women (PMW). However, the interactions between exercise training and bone mineral density are not completely understood. We evaluated the effects of physical exercise on BMD in women aged ≥ 60 years postmenopausal.This systematic review and meta-analysis sets out to determine the effects of physical exercise on BMD in older postmenopausal women.A systematic search was conducted in Medline, Science Direct, Cochrane, PubMed, CINAHL, Google Scholar, Scopus, and ProQuest up to December 25, 2021. Fifty-three studies, which assessed a total of 2896 participants (mean age: between 60 and 82 years), were included and analyzed using a random-effects model to estimate weighted mean differences (WMD) with 95% confidence intervals (CI).The meta-analysis found that exercise training significantly (p 0.05) increased femoral neck (WMD: 0.01 g/cmOur findings suggest that exercise training may improve bone mineral density in older PMW. This improvement is mediated by increases in the femoral neck, lumbar spine, and trochanter BMD. Further long-term studies are required to confirm these findings.

Postmenopausal osteoporosis (PMOP) therapies are frequently evaluated by bone mineral density (BMD) gains against patients receiving placebo (calcium and vitamin D supplementation, a mild bone turnover-suppressing intervention), which is not equivalent to either healthy or treatment-naive PMOP. The aim of the present observational study was to assess the effects of TPTD treatment in PMOP (20 μg, once daily) at 6 (TPTD 6m; n = 28, age 65 ± 7.3 years), and 24 (TPTD 24m; n = 32, age 67.4 ± 6.15 years) months on bone quality indices at actively forming trabecular surfaces (with fluorescent double labels). Data from the TPTD-treated PMOP patients were compared with those in healthy adult premenopausal women (HC; n = 62, age 40.5 ± 10.6 years), and PMOP receiving placebo (PMOP-PLC; n = 94, age 70.6 ± 4.5 years). Iliac crest biopsies were analyzed by Raman microspectroscopy at three distinct tissue ages: mid-distance between the second label and the bone surface, mid-distance between the two labels, and 1 μm behind the first label. Mineral to matrix ratio (MM), mineral maturity/crystallinity (MMC), tissue water (TW), glycosaminoglycan (GAGs), and pyridinoline (Pyd) content were determined. Outcomes were compared by ANCOVA with subject age and tissue age as covariates, and health status as a fixed factor, followed by Sidak's post-hoc testing (significance assigned to p 0.05). Both TPTD groups increased MM compared to PMOP-PLC. While TPTD 6m had values similar to HC, TPTD 24m had higher values compared to either HC or TPTD 6m. Both TPTD groups had lower MMC values compared to PMOP-PLC and similar to HC. TPTD 6m patients had higher TW content compared to HC, while TPTD 24m had values similar to HC and lower than either PMOP-PLC or TPTD 6m. Both TPTD groups had lower GAG content compared to HC group, while TPTD 6m had higher values compared to PMOP-PLC. Finally, TPTD 6m patients had higher Pyd content compared to HC and lower compared to PMOP-PLC, while TPTD 24m had lower values compared to PMOP-PLC and TPTD 6m, and similar to HC group. The results of the present study indicate that effects of TPTD on forming trabecular bone quality indices depend on treatment duration. At the recommended length of 24 m, TPTD restores bone mineral and organic matrix quality indices (MMC, TW, Pyd content) to premenopausal healthy (HC) levels.

Introduction Denosumab is commonly used to treat osteoporosis. However, discontinuation results in rebound bone loss and increased vertebral fracture risk. We report a clinical case series, illustrating the dilemma in deciding the best treatment should denosumab be stopped. Cases In eight patients aged 56-89 years, zolendronic acid after stopping denosumab resulted in BTM rises and BMD decline.  In a 68-year-old, two years of oral bisphosphonate after three years of denosumab resulted in elevated bone turnover markers (BTM) and decline in bone mineral density (BMD), necessitating a switch to zoledronic acid.  In a 79-year-old, two annual doses of zolendronic acid after three years of denosumab failed to suppress high BTM, with BMD dropping and denosumab being restarted.  In a 60-year-old, on stopping denosumab after 10 years of oral bisphosphonate, BMD remained stable despite no further therapy. Conclusion Drug holidays are not an option with denosumab, with a risk of bone loss even on transitioning to bisphosphonates. Risk is greater with longer duration of treatment6 and may be mitigated by prior bisphosphonate use. Standard dose zoledronic acid does not prevent bone loss in a significant proportion of patients. BTM may help in monitoring treatment and need for further bisphosphonates.

This study was performed to evaluate quality of life (QOL) and patient satisfaction with raloxifene/cholecalciferol combination therapy in postmenopausal women with low bone mass. This multicenter, prospective, noninterventional observational study included 3907 postmenopausal women who received a combination of raloxifene 60 mg and cholecalciferol 800 IU daily to treat or prevent osteoporosis. Changes in QOL and patient satisfaction were evaluated after 3 and 6 months of treatment. In addition, the safety profile was assessed. Mean age was 67.7 ± 9.3 years old. QOL, assessed by European Quality of life instrument 5 Dimensions (EQ-5D) index, improved significantly after 3 months (0.81 ± 0.11, P P P P P

Both osteoporosis with related fragility fractures and cardiovascular diseases are rapidly outspreading worldwide. Since they are often coexistent in elderly patients and may be related to possible common pathogenetic mechanisms, the possible reciprocal effects of drugs employed to treat these diseases have to be considered in clinical practice. Bisphosphonates, the agents most largely employed to decrease bone fragility, have been shown to be overall safe with respect to cardiovascular diseases and even capable of reducing cardiovascular morbidity in some settings, as mainly shown by real life studies. No randomized controlled trials with cardiovascular outcomes as primary endpoints are available. While contradictory results have emerged about a possible BSP-mediated reduction of overall mortality, it is undeniable that these drugs can be employed safely in patients with high fracture risk, since no increased mortality has ever been demonstrated. Although partial reassurance has emerged from meta-analysis assessing the risk of cardiac arrhythmias during bisphosphonates treatment, caution is warranted in administering this class of drugs to patients at risk for atrial fibrillation, possibly preferring other antiresorptives or anabolics, according to osteoporosis guidelines. This paper focuses on the complex relationship between bisphosphonates use and cardiovascular disease and possible co-management issues.

Poor medication adherence of osteoporosis patients is a major global medical problem because of its negative impact on health outcomes and quality of life. The aim of this study was to evaluate how differences in dosing regimens influence adherence to oral bisphosphonates using data from a large health insurance provider in Japan. This was a retrospective observational study using claims data obtained between October 2012 and January 2018, from the community-based National Health Insurance program of a large city in Japan. The data included in the analysis were obtained from women 60 to 74 years old whose oral bisphosphonate prescription was detected between April 2013 and February 2017. Treatment adherence was monitored from the initial prescription for one year, i.e., up to January 2018. Primary comparisons among the daily-dosing, weekly-dosing, and monthly-dosing groups were based on the mean medication possession ratio (MPR). Data from a total of 3,958 patients were analyzed. The numbers of patients aged 60-64, 65-69, and 70-74 were 425, 1,400, and 2,133, respectively. The highest mean MPR was 69.4% for the monthly-dosing of bisphosphonates, followed by the weekly-dosing at 63.5%, and daily-dosing at 57.2%. Using the Kruskal-Wallis test with Dunn-Bonferroni correction, there were significant differences in mean MPR for daily versus weekly (p < 0.01), daily versus monthly (p < 0.001), and weekly versus monthly dosing regimens (p < 0.05). These results suggest significantly more patients adhere to a monthly or weekly regimen of bisphosphonates in the treatment of osteoporosis than to a daily regimen.

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling‐based formation (MBF), remodeling‐based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open‐label, single‐arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5‐, 5.2‐, 2.8‐, and 12.9‐fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p

Rationale: Postmenopausal-induced bone loss is mainly caused by declining core transcription factors (TFs) of bone mesenchymal stem cells (BMSCs), but little is known about how miRNAs regulate chromatin structure remodeling of TFs gene to maintain BMSCs function in bone homeostasis. Methods: We examined the serum, salivary and bone samples from Pre- and Post-menopause women by paired analysis and confirmed canonical ceRNA role of MIR143HG and miR-143/145 complexes in cytoplasm and noncanonical role for SOX2 transcription in nucleus (FISH, qRT-PCR, immunostaining, Luciferase assays and ChIP). Moreover, we took advantage of transgenic mice under OVX-induced osteoporosis, studying the in vitro and in vivo effect of miR-143/145 deletion on BMSCs function and bone homeostasis. Last, using miRNA antagonism, antagomiR-143/145 were delivered into bone marrow to treat estrogen-deficient bone loss. Results: Here, we identified miR-143/145 as potential diagnostic candidates for postmenopausal osteoporosis, and miR-143/145 overexpression impaired BMSCs self-renewing and differentiation function. Mechanistically, we confirmed that cytoplasmic miR-143/145 and LncRNA MIR143HG, that controlled by ERβ, cooperatively regulated pluripotency genes translation via canonical ceRNA pathway, and MIR143HG cooperates with miR‑143 to nuclear translocation for co-activation of SOX2 transcription via opening promoter chromatin. Meanwhile, miR‑143/145 were shuttled into osteoclasts in extracellular vesicles and triggered osteoclastic activity by targeting Cd226 and Srgap2. Furthermore, miR-143/145-/- mice or using chemically‑modified antagomiR-143/145 significantly alleviated estrogen-deficient osteoporosis. Conclusions: Our findings reveal a canonical and noncanonical role of miR-143/145 in controlling BMSCs pluripotency and unfold their dual effect on bone formation and bone resorption, suggesting miR-143/145 as promising therapeutic targets for treating estrogen-deficient bone loss.

The association between Coronary Artery Calcification (CAC) and osteoporosis has been reported but not fully understood. Therefore, using an original bioinformatic framework we analyzed transcriptomic profiles of 20 elderly women with high CAC score and 31 age- and sex-matching controls from Sao Paulo Ageing & Health study (SPAH). We integrated differentially expressed microRNA (miRNA) and long-noncoding RNA (lncRNA) interactions with coding genes associated with CAC, in the context of bone-metabolism genes mined from literature. Top non-coding regulators of bone metabolism in CAC included miRNA 497-5p/195 and 106a-5p, and lncRNA FAM197Y7. Top non-coding RNAs revealed significant interplay between genes regulating bone metabolism, vascularization-related processes, chromatin organization, prostaglandin and calcium co-signaling. Prostaglandin E2 receptor 3 (PTGER3), Fibroblasts Growth Factor Receptor 1 (FGFR1), and One Cut Homeobox 2 (ONECUT2) were identified as the most susceptible to regulation by the top non-coding RNAs. This study provides a flexible transcriptomic framework including non-coding regulation for biomarker-related studies.

Aims/Introduction Patients with type 2 diabetes mellitus have a higher bone fracture risk than patients without diabetes. Although denosumab (Dmab) is a potent bone resorption inhibitor, its efficacy in patients with type 2 diabetes mellitus has not been elucidated. In this study, we investigated the effects of switching to Dmab from bisphosphonates (BP) or a selective estrogen receptor modulator (SERM) in postmenopausal type 2 diabetes mellitus patients. Materials and Methods This was a three medical institutions, prospective, observational study for postmenopausal patients with type 2 diabetes mellitus whose T‐score of femoral neck or lumbar spine bone mineral density was under −1.0 standard deviation, even after >6 months of BP or SERM administration. After obtaining consent, participants were treated for osteopenia/osteoporosis by either continuing BP (BP‐BP group)/SERM (SERM‐SERM group), or by switching to Dmab (BP‐Dmab or SERM‐Dmab groups). Changes in bone mineral density and bone metabolism marker levels were evaluated after 6 months. Results A total of 48 patients were included in this study, and each group comprised 12 patients. No significant difference existed in baseline characteristics among the groups. The average age and glycated hemoglobin were 71 ± 8 years and 7.2 ± 0.9%, respectively. In the SERM‐Dmab group, lumbar spine bone mineral density was significantly increased by 5.0% compared with the SERM‐SERM group (P, We showed more favorable effects of denosumab on bone metabolism compared with bisphosphonates or selective estrogen receptor modulator alone in postmenopausal patients with type 2 diabetes mellitus. Switching from bisphosphonates or selective estrogen receptor modulator to denosumab provides an effective treatment strategy to prevent the progression in postmenopausal patients with type 2 diabetes mellitus who are still in the osteopenia or osteoporosis state after treatment with bisphosphonates or selective estrogen receptor modulator and active vitamin D.

Miika Värri,1 Leo Niskanen,2 Tomi-Pekka Tuomainen,3 Risto Honkanen,1,4 Heikki Kröger,1,5 Marjo T Tuppurainen1,6 1Kuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 2Department of Endocrinology and Metabolism, Abdominal Centre, Helsinki University Hospital, Universities of Helsinki and Eastern Finland, Helsinki, Finland; 3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 4Lapland Hospital District, Rovaniemi, Finland; 5Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland; 6Department of Obstetrics and Gynaecology, Kuopio University Hospital, Kuopio, FinlandCorrespondence: Miika VärriKuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, FinlandTel +358503655083Fax +358 17 172 611Email mvarri@uef.fiPurpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association.Patients and Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (1H) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV).Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean ± SD: 0.033 ± 0.0070; group II: 0.041 ± 0.014, CI95%: 0.018‒0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p> 0.05).Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.Keywords: metabolomics, carotid artery calcification, postmenopausal women, osteoporosis, carotid intima-media thickness, acetate

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22–2.07; P r = − 0.180; P P

Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA-seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP-2) expression, upregulated osteoclast-specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR-378, which in turn targeted BMP-2 via bioinformatics analysis and the dual-luciferase reporter assay. Transfection of the miR-378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR-378/BMP-2 signaling pathway. Targeting the circ_0007059/miR-378/BMP-2 axis is possibly a novel idea in osteoporosis treatment.

Osteoporosis is a condition affecting millions of Americans, the majority of which are women secondary to low estrogen in the postmenopausal state. In many instances, the diagnosis is not recognized until after a fracture has occurred due to the "silent" nature of this disease. As a result, this leads to millions of fractures each year, placing a substantial economic burden of billions of dollars from Medicare alone. Prevention, early diagnosis, and treatment remain paramount in reducing this economic impact as well as improving overall incidence of mortality and morbidity. Goals of care include preventing the progression of disease and minimizing bone fractures, particularly in the hips, spine, and wrists. This article will examine the risks of osteoporosis and osteoporotic fractures in postmenopausal women, the current and emerging pharmacologic treatment options, and the role of managed care pharmacists in decreasing economic burden and improving patient care.

Malabsorption due to celiac disease (CD) may contribute to postmenopausal osteoporosis. This study aimed to survey participants with CD regarding their bone density, fractures, and bone-preserving medications; to compare tolerance of bone-preserving medications in participants with and without CD; and to review the evidence for CD screening and osteoporosis therapies in the setting of CD. We recruited 131 participants with CD and 102 participants without CD. Of those with CD, 87% were diagnosed in adulthood and 40% had no recognized gastrointestinal symptoms. In 21% CD was diagnosed after the diagnosis of osteoporosis and in 9% after a fracture. No difference was found in the tolerability of bone medications between participants with CD and those without. Review of the literature found that, although monitoring of bone health is recommended for patients with CD, screening for CD is not generally accepted for patients with osteoporosis, although studies of the prevalence of CD in osteoporosis had incomplete ascertainment methods. There is a lack of well-conducted studies and therefore insufficient data for the efficacy and tolerability of bone medication in CD. In conclusion, both CD and menopause lead to bone loss. Identifying CD in postmenopausal women should lead to modification of osteoporosis management.