Fracture risk assessment in the presence of competing risk of death.

PURPOSE: To identify the optimal statistical approach for predicting the risk of fragility fractures in the presence of competing event of death. METHODS: We used real-world data from the Dubbo Osteoporosis Epidemiology Study that has monitored 3035 elderly participants for bone health and mortality. Fragility fractures were ascertained radiologically. Mortality was confirmed by the State Registry. We considered four statistical models for predicting fracture risk: (i) conventional Cox's proportional hazard model, (ii) cause-specific model, (iii) Fine-Gray sub-distribution model, and (iv) multistate model. These models were fitted and validated in the development (60% of the original sample) and validation (40%) subsets, respectively. The model performance was assessed by discrimination and calibration analyses. RESULTS: During a median follow-up of 11.3 years (IQR: 7.2, 16.2), 628 individuals (34.5%) in the development cohort fractured, and 630 (34.6%) died without a fracture. Neither the discrimination nor the 5-year prediction performance was significantly different among the models, though the conventional model tended to overestimate fracture risk (calibration-in-the-large index = - 0.24; 95% CI: - 0.43, - 0.06). For 10-year risk prediction, the multistate model (calibration-in-the-large index = - 0.05; 95% CI: - 0.20, 0.10) outperformed the cause-specific (- 0.23; - 0.30, - 0.08), Fine-Gray (- 0.31; - 0.46, - 0.16), and conventional model (- 0.54; - 0.70, - 0.39) which significantly overestimated fracture risk. CONCLUSION: Adjustment for competing risk of death has minimum impact on the short-term prediction of fracture. However, the multistate model yields the most accurate prediction of long-term fracture risk and should be considered for predictive research in the elderly, who are also at high mortality risk. Fracture risk assessment might be compromised by the competing event of death. This study, using real-world data found a multistate model was superior to the current competing risk methods in fracture risk assessment. A multistate model is considered an optimal statistical method for predictive research in the elderly.

Sex-differential testosterone response to long-term weight loss.

OBJECTIVES: Obesity-associated gonadal dysfunction is a common comorbidity in patients seeking weight loss interventions. We examined the incremental effect of weight loss on gonadal axes in men and women over 3 years. Changes in sex hormones were compared between dietary intervention (Diet) and bariatric procedures: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and laparoscopic adjustable gastric banding (LAGB). Additional analysis assessed changes in corticotropic, somatotropic and thyroid axes after weight loss interventions. METHODS: This prospective, observational study included 61 adults with Body Mass Index >30 kg/m2, mean age 51 (SD = 11) years. Endocrine parameters were measured at baseline and at 6 timepoints over 36-months. RESULTS: For each 1 kg of weight lost, between baseline and 36 months, total testosterone increased by 0.6% (95% CI: 0.2%, 1.0%, p = 0.002) in males and decreased by 0.8% (95% CI: -1.4%, -0.3%, p = 0.003) in females. These changes remained statistically significant when controlled for age and for menopausal status in females. At 36 months, in comparison with Diet, RYGB women had lower total testosterone by 54% (95% CI: -90%, -17%, p = 0.004), reduced free androgen index (FAI) by 65% (95% CI; -114%, -17%, p = 0.009) while SG had reduced FAI by 39% (95% CI; -77%, 0%, p = 0.05). No such differences between groups were noted for male subjects. Adrenocorticotropic hormone declined by 0.3% (95% CI: 0.0, -0.5%, p = 0.05), insulin-like growth factor-1 increased by 0.4% (95% CI; 0.2%, 0.7%, p = 0.005), without such thyrotrophin change for each 1 kg of weight loss, for entire cohort, over 36 months. CONCLUSIONS: The testosterone changes observed in this study were proportional to the amount of weight loss. In females, reduction in androgens was independent of age and menopausal status and more pronounced after bariatric procedures. This study finding warrants further clinical research to explore an impact of androgen reduction on functional and cognitive status in postmenopausal women. The observed changes in pituitary hormones may contribute to the metabolic benefits of bariatric surgery.

Multimorbidity clusters potentially superior to individual diseases for stratifying fracture risk in older people: a nationwide cohort study.

RATIONALE: Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk. METHODS: This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50 years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively. RESULTS: The study included 793 815 men (age: 64 ± 10) and 873 524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14 years (IQR: 6.5, 14), 95 372 men and 212 498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices. CONCLUSIONS: Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices.

Bone metabolism in diabetes: a clinician's guide to understanding the bone-glucose interplay.

Skeletal fragility is an increasingly recognised, but poorly understood, complication of both type 1 and type 2 diabetes. Fracture risk varies according to skeletal site and diabetes-related characteristics. Post-fracture outcomes, including mortality risk, are worse in those with diabetes, placing these people at significant risk. Each fracture therefore represents a sentinel event that warrants targeted management. However, diabetes is a very heterogeneous condition with complex interactions between multiple co-existing, and highly correlated, factors that preclude a clear assessment of the independent clinical markers and pathophysiological drivers for diabetic osteopathy. Additionally, fracture risk calculators and routinely used clinical bone measurements generally underestimate fracture risk in people with diabetes. In the absence of dedicated prospective studies including detailed bone and metabolic characteristics, optimal management centres around selecting treatments that minimise skeletal and metabolic harm. This review summarises the clinical landscape of diabetic osteopathy and outlines the interplay between metabolic and skeletal health. The underlying pathophysiology of skeletal fragility in diabetes and a rationale for considering a diabetes-based paradigm in assessing and managing diabetic bone disease will be discussed.

Osteoporosis screening in Australian community pharmacies: A mixed methods study.

ISSUES ADDRESSED: Osteoporosis and poor bone health impact a large proportion of the Australian population, but is drastically underdiagnosed and undertreated. Community pharmacies are a strategic location for osteoporosis screening services due to their accessibility and the demographic profile of customers. The aim of this study was to develop, implement and evaluate a community pharmacy health promotion service centred on encouraging consumers to complete an anonymous osteoporosis screening survey called Know Your Bones. METHODS: The implementation process was documented using the REAIM (reach, effectiveness, adoption, implementation, maintenance) framework. Uptake of the Know Your Bones screening tool was monitored anonymously with website traffic. Surveys and interviews were designed to capture consumer outcomes after screening. Semi-structured interviews were conducted with Australian community pharmacy stakeholders during design and implementation phases to explore their perspectives of the barriers and facilitators. RESULTS: The service was implemented in 27 community pharmacies. There were 448 visits to the screening website. Interviews were conducted with 41 stakeholders. There were a range of factors that appeared to influence implementation of the service. Perceived acceptability was critical, which depended on staff training, pharmacists' altruism, and remuneration. Staff relied heavily on their existing close relationships with consumers. No consumers completed non-anonymous surveys or agreed to participate in interviews post-screening. CONCLUSION: Using an implementation science approach, a community pharmacy osteoporosis screening service for the Australian context was designed and found to be acceptable to pharmacy staff and effective in reaching the target population. SO WHAT?: This low-cost and non-invasive health promotion has potential to sustainably increase national screening rates for osteoporosis.

Health Perceptions, Multimorbidity, and New Fractures and Mortality Among Patients With a Fracture.

Importance: A high proportion of patients who sustain a fracture have multimorbidity. However, the association of multimorbidity with postfracture adverse outcomes, such as subsequent fractures and premature mortality, has not been widely explored. Objective: To examine the association of multimorbidity and self-rated health with subsequent fractures and mortality after fracture. Design, Setting, and Participants: This prospective cohort study included participants from New South Wales, Australia, in the Sax Institute's 45 and Up Study (n = 267 357). Participants were recruited from July 2005 to December 2009 and followed up from the date of the incident fracture until subsequent fracture, death, or the end of the study (April 2017), whichever occurred first, with questionnaire data linked to hospital admission and medication records. Data analysis was reported between March and September 2023. Exposures: Charlson Comorbidity Index (CCI) score and self-rated health (SRH). Main Outcomes and Measures: The main outcomes were subsequent fracture or mortality after an incident fracture. Associations between SRH measures and subsequent fracture and mortality were also assessed. All analyses were stratified by sex given the different fracture and mortality risk profiles of females and males. Results: Of 25 280 adults who sustained incident fractures, 16 191 (64%) were female (mean [SD] age, 74 [12] years) and 9089 (36%) were male (mean [SD] age, 74 [13] years). During a median follow-up time of 2.8 years (IQR, 1.1-5.2 years), 2540 females (16%) and 1135 males (12%) sustained a subsequent fracture and 2281 females (14%) and 2140 males (24%) died without a subsequent fracture. Compared with a CCI score of less than 2, those with a CCI score of 2 to 3 had an increased risk of subsequent fracture (females: hazard ratio [HR], 1.16 [95% CI, 1.05-1.27]; males: HR, 1.25 [95% CI, 1.09-1.43]) and mortality (females: HR, 2.19 [95% CI, 1.99-2.40]; males: HR, 1.89 [95% CI, 1.71-2.09]). Those with a CCI score of 4 or greater had greater risks of subsequent fracture (females: HR, 1.33 [95% CI, 1.12-1.58]; males: HR, 1.48 [95% CI, 1.21-1.81]) and mortality (females: HR, 4.48 [95% CI, 3.97-5.06]; males: HR, 3.82 [95% CI 3.41-4.29]). Self-rated health was also significantly associated with subsequent fracture and mortality. Those reporting the poorest health and quality of life had the highest subsequent fracture risks, and their mortality risks were even higher. Conclusions and Relevance: In this cohort study, both CCI and SRH measures were associated with increased risk of subsequent fractures and mortality after fracture, underscoring the importance of managing the care of patients with comorbidities who sustain a fracture.

Temporal patterns of osteoclast formation and activity following withdrawal of RANKL inhibition.

Rebound bone loss following denosumab discontinuation is an important clinical challenge. Current treatment strategies to prevent this fail to suppress the rise and overshoot in osteoclast-mediated bone resorption. In this study, we use a murine model of denosumab treatment and discontinuation to show the temporal changes in osteoclast formation and activity during RANKL inhibition and withdrawal. We show that the cellular processes that drive the formation of osteoclasts and subsequent bone resorption following withdrawal of RANKL inhibition precede the rebound bone loss. Furthermore, a rise in serum TRAP and RANKL levels is detected before markers of bone turnover used in current clinical practice. These mechanistic advances may provide insight into a more defined window of opportunity to intervene with sequential therapy following denosumab discontinuation.

Stopping denosumab, a medication commonly used to improve bone mass by blocking formation of bone resorbing osteoclasts, leads to a rebound loss in the bone which was gained during treatment. Current strategies to prevent this bone loss fail in most cases as they are unable to prevent the rise and overshoot in bone resorption by osteoclasts. Thie stems from an incomplete understanding of how osteoclasts behave during denosumab treatment and after treatment is discontinued. We use a mouse model of this phenomenon to show how osteoclast formation and activity changes throughout this process. We show that increases in the processes that drive the formation of osteoclasts can be detected in the circulation before bone loss occurs. These findings could therefore provide insight into a targeted 'window of opportunity' to intervene and prevent the rebound bone loss following stopping denosumab in patients.

Association between Fat Mass and Obesity-Related Transcript Polymorphisms and Osteoporosis Phenotypes.

BACKGROUND: Common variants in the fat mass and obesity-related transcript (FTO) gene are related to body mass index and obesity, suggesting its potential association with bone mineral density (BMD) and fracture risk. This study sought to define the association between FTO gene variants and the following phenotypes: (1) BMD; (2) bone loss; and (3) fracture risk. METHODS: This analysis was based on the Dubbo Osteoporosis Epidemiology Study that included 1,277 postmenopausal women aged ≥60 years living in Dubbo, Australia. BMD at the femoral neck and lumbar spine was measured biennially by dual energy X-ray absorptiometry (GE Lunar). Fractures were radiologically ascertained. Six single nucleotide polymorphisms (SNPs; rs1421085, rs1558902, rs1121980, rs17817449, rs9939609, and rs9930506) of the FTO gene were genotyped using TaqMan assay. RESULTS: Women homozygous for the minor allele (GG) of rs9930506 had a significantly higher risk of hip fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.15-3.23) than those homozygous for the major allele (AA) after adjusting for potential confounding effects. Similar associations were also observed for the minor allele of rs1121980. However, there was no significant association between the FTO SNPs and BMD or the rate of bone loss. CONCLUSIONS: Common variations in the FTO gene are associated with a hip fracture risk in women, and the association is not mediated through BMD or bone loss.

Effect of denosumab on inflammation and bone health in active Charcot foot: A phase II randomised controlled trial.

AIMS: We aimed to investigate the effect of denosumab on pedal bone health and clinical resolution in active Charcot foot (CN). METHODS: This multicentre open-label phase 2 randomised controlled trial recruited adults with diabetes mellitus and active CN within 3 months of onset. Participants were randomised to standard care alone, or with denosumab 60 mg subcutaneously. Denosumab was administered at baseline and again at 6 months, unless foot temperature had normalised (i.e. <2 °C compared to contralateral foot). Co-primary outcomes were change in calcaneal Stiffness Index and foot temperature normalisation over 18 months. RESULTS: Twelve participants per group were analysed; mean age 58 ± 11 years, 83 % male and 92 % had type 2 diabetes. Active CN duration was median 8 (IQR 7-12) weeks. Ninety-two percent were Eichenholtz stage 1 and 96 % involved the midfoot. After 1-month, median decline in Stiffness Index was less in the denosumab verses standard care group (0.5 [IQR -1.0 to 3.9] vs -2.8 [-8.5 to -1.0], p = 0.008). At 18-months, 92 % of the denosumab group attained foot temperature normalisation versus 67 % of the standard care group (p = 0.13). CONCLUSIONS: Denosumab ameliorated the early decline in calcaneal Stiffness Index associated with active CN. However, no difference in normalisation of foot temperature was observed.

Teriparatide as Treatment for Severe Osteoporosis in Lung Transplant Recipients.

Osteoporosis and osteopenia are common in lung transplant (LTx) recipients, with a significantly increased incidence compared to other non-lung solid organ transplant patients. Despite high fracture rates, including in patients treated with antiresorptive medications, there are limited data on the use of anabolic treatments in LTx recipients. We present clinical, biochemical and bone mineral density data for 3 patients with severe osteoporosis treated with teriparatide 20 micrograms daily for 18 months post-LTx. Prednisone doses ranged between 5 and 10 mg daily throughout the treatment period. All patients had previously received zoledronate (last dose 12-24 months prior to teriparatide). Bone turnover was monitored repeatedly during treatment in one patient. Following completion of teriparatide, all patients received consolidation treatment with 4 mg zoledronate. Bone density was measured prior and within 6 to 12 months after completion of teriparatide. All 3 patients experienced an increase in bone density at the lumbar spine (median +12%; range, 2%-14%) and total proximal femur (median +8%, range, 8%-10%). No adverse effects were observed. Given that severe osteoporosis is highly prevalent in LTx patients, teriparatide should be further studied as a treatment in this clinical setting. Our cases suggest it is safe and effective.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women.

Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference - 69%, 95% CI - 127% to - 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.Trial registration: ACTRN12617000545369, registered 18th April 2017.

Patient Self-Assessment of Walking Ability and Fracture Risk in Older Australian Adults.

Importance: The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated. Objective: To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture. Design, Setting, and Participants: This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023. Exposure: Self-reported walking limitation. Main Outcomes and Measures: Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures). Results: Among the 266 912 participants enrolled in the 45 and Up Study, 238 969 were included, with 126 015 (53%) women (mean [SD] age, 63 [11] years) and 112 954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39 324 women [24%]; 23 191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase. Conclusions and Relevance: In this cohort study of 238 969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.

Establishing consensus recommendations for long-term osteoporosis care for patients who have attended an Australian fracture liaison service: a Delphi study.

Coordinating healthcare activities between fracture liaison services (FLS) and primary care is challenging. Using a Delphi technique, we developed 34 consensus statements to support improved care coordination across this healthcare transition. PURPOSE: Evidence supporting an optimal coordination strategy between fracture liaison services (FLS) and primary care is lacking. This study aimed to develop consensus statements to support consistency and benchmarking of clinical practice to improve coordination of care for patients transitioning from FLS to primary care following an osteoporotic fracture. METHODS: A Delphi technique was used to develop consensus among a panel of experts, including FLS clinicians (medical and non-medical), general practitioners (GPs), and consumers. RESULTS: Results of a preparatory questionnaire (n = 33) informed the development of 34 statements for review by expert panellists over two Delphi rounds (n = 25 and n = 19, respectively). The majority of participants were from New South Wales (82%), employed as FLS clinicians (78.8%) and working in metropolitan centres (60.6%). Consensus was achieved for 24/34 statements in round one and 8/10 statements in round two. All statements concerning patient education, communication, and the GP-patient relationship achieved consensus. Expert opinions diverged in some areas of clinician roles and responsibilities and long-term monitoring and management recommendations. CONCLUSION: We found clear consensus among experts in many key areas of FLS integration with primary care. While experts agreed that primary care is the most appropriate setting for long-term osteoporosis care, overall confidence in primary care systems to achieve this was low. The role of (and responsibility for) adherence monitoring in a resource-limited setting remains to be defined.

Denosumab and Mortality in a Real-World Setting: A Comparative Study.

Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the association between Dmab and all-cause mortality compared with no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from the Sax Institute's 45 and Up Study (n = 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). The new-user cohort design with propensity-score (PS) matching was implemented. In the fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men; oral BPs: 615 women, 266 men). In the no-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs: 479 men, 1534 women; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex-specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [CI] 0.36-0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR = 0.56, 95% CI 0.42-0.77; men HR = 0.56, 95% CI 0.40-0.78). In the no-fracture cohort, compared with BPs, Dmab was associated with 1.5- to 2.5-fold higher mortality than oral BPs (women HR = 1.49, 95% CI 1.13-1.98; men HR = 2.74; 95% CI 1.82-4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had generally higher mortality than oral BP users in those without fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).

Associations of Type 2 Diabetes, Body Composition, and Insulin Resistance with Bone Parameters: The Dubbo Osteoporosis Epidemiology Study.

Type 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross-sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA-IR]

Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management reviews in primary care.

INTRODUCTION: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia's Home Medicine Review (HMR) can reduce patients' intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF. METHOD AND ANALYSIS: Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants' cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care. ETHICS AND DISSEMINATION: Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up. TRIAL REGISTRATION NUMBER: ACTRN12622000261718.