Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Development and validation of the risk engine for an Australian Health Economics Model of Osteoporosis.

The Australian Health Economics Model of Osteoporosis (AusHEMO) has shown good face, internal and cross validities, and can be used to assist healthcare decision-making in Australia. PURPOSE: This study aimed to document and validate the risk engine of the Australian Health Economics Model of Osteoporosis (AusHEMO). METHODS: AusHEMO is a state-transition microsimulation model. The fracture risks were simulated using fracture incidence rates from the Dubbo Osteoporosis Epidemiology Study. The AusHEMO was validated regarding its face, internal and cross validities. Goodness-of-fit analysis was conducted and Lin's coefficient of agreement and mean absolute difference with 95% limits of agreement were reported. RESULTS: The development of AusHEMO followed general and osteoporosis-specific health economics guidelines. AusHEMO showed good face validity regarding the model's structure, evidence, problem formulation and results. In addition, the model has been proven good internal and cross validities in goodness-of-fit test. Lin's coefficient was 0.99, 1 and 0.94 for validation against the fracture incidence rates, Australian life expectancies and residual lifetime fracture risks, respectively. CONCLUSIONS: In summary, the development of the risk engine of AusHEMO followed the best practice for osteoporosis disease modelling and the model has been shown to have good face, internal and cross validities. The AusHEMO can be confidently used to predict long-term fracture-related outcomes and health economic evaluations when costs data are included. Health policy-makers in Australia can use the AusHEMO to select which osteoporosis interventions such as medications and public health interventions represent good value for money.

Current status and distribution of hip fractures among older adults in China.

China is a middle-risk country for hip fracture at present, which differs from previous data that it was low-risk. By 2050, the total number of hip fractures in people older than 65 years is predicted to be 1.3 million. INTRODUCTION: To assess hip fracture incidence in China and examine the heterogeneity of hip fracture in seven geographical regions of China. METHODS: There were 238,230 hip fracture patients aged 65 years or older from 2013 to 2016 from a large national in-patients database (HQMS) involving 30.6 million hospitalizations. Taking into account the total national hospitalization rate per calendar year, we estimated the incidence of hip fracture per 100,000 residents older than 65 years in China overall and in seven geographical Chinese regions. RESULTS: The proportion of men and women older than 65 years with hip fractures was 1.00:1.95. Between 2013 and 2016, the number of hip fractures per 100,000 people age 65+ was 278. China has vast territories; the number of hip fractures per 100,000 people over 65 years old was 202 in Northeast China and 374 in Northwest China. Northwest has higher altitude, lower population density, is less developed with lower urbanization than Northeast China which is low altitude, and highly urbanized. CONCLUSIONS: China should no longer be regarded as a low-risk country for hip fracture. By 2050, the total number of hip fractures in people older than 65 years in China is predicted to be 1.3 million. Higher altitude areas had higher hip fracture rates than lower altitude, higher urbanized areas.

Assessing the clinical utility of genetic profiling in fracture risk prediction: a decision curve analysis.

Using decision curve analysis on 2188 women and 1324 men, we found that an osteogenomic profile constructed from 62 genetic variants improved the clinical net benefit of fracture risk prediction over and above that of clinical risk factors and BMD. INTRODUCTION: Genetic profiling is a promising tool for assessing fracture risk. This study sought to use the decision curve analysis (DCA), a novel approach to determine the impact of genetic profiling on fracture risk prediction. METHODS: The study involved 2188 women and 1324 men, aged 60 years and above, who were followed for up to 23 years. Bone mineral density (BMD) and clinical risk factors were obtained at baseline. The incidence of fracture and mortality were recorded. A weighted individual genetic risk score (GRS) was constructed from 62 BMD-associated genetic variants. Four models were considered: CRF (clinical risk factors); CRF + GRS; Garvan model (GFRC) including CRF and femoral neck BMD; and GFRC + GRS. The DCA was used to evaluate the clinical net benefit of predictive models at a range of clinically reasonable risk thresholds. RESULTS: In both women and men, the full model GFRC + GRS achieved the highest net benefits. For 10-year risk threshold > 18% for women and > 15% for men, the GRS provided net benefit above those of the CRF models. At 20% risk threshold, adding the GRS could help to avoid 1 additional treatment per 81 women or 1 per 24 men compared with the Garvan model. At lower risk thresholds, there was no significant difference between the four models. CONCLUSIONS: The addition of genetic profiling into the clinical risk factors can improve the net clinical benefit at higher risk thresholds of fracture. Although the contribution of genetic profiling was modest in the presence of BMD + CRF, it appeared to be able to replace BMD for fracture prediction.

Early changes in bone turnover and inflammatory biomarkers and clinically significant bone mineral density loss over 48 weeks among HIV-infected patients with virological failure of a standard first-line antiretroviral therapy regimen in the SECOND-LINE study.

OBJECTIVES: We assessed whether changes at week 12 in markers of bone turnover, inflammation, and immune activation were associated with clinically important (≥ 5%) bone mineral density (BMD) loss from baseline to week 48 at the proximal femur (hip) and lumbar spine in the SECOND-LINE study. METHODS: We measured concentrations of procollagen type 1 pro-peptide (P1NP), carboxyl-terminal collagen crosslinks (CTX), high-sensitivity C-reactive protein (hs-CRP), D-dimer, interleukin (IL)-6, tumor necrosis factor (TNF), neopterin, and soluble CD14 and 163 at weeks 0, 12, and 48 in 123 SECOND-LINE dual-energy X-ray absorptiometry (DXA) substudy participants. Linear regression was used to compare changes in biomarkers. Predictors of ≥ 5% BMD loss were examined using multivariable regression. RESULTS: The mean age was 38 years, the mean CD4 T-cell count was 252 cells/µL and the mean viral load was 4.2 log HIV-1 RNA copies/mL; 56% of participants were female and 47% were randomized to receive a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI]-based regimen [91% (53/58) were randomized to receive a tenofovir disoproxil fumarate (TDF)-containing regimen]. Over 48 weeks, 71% in the N(t)RTI arm experienced ≥ 5% hip BMD loss vs. 29% in the raltegravir arm (P = 0.001). Week 12 changes in P1NP and CTX were significantly greater among patients experiencing ≥ 5% hip BMD loss, patients randomized to N(t)RTI, and male patients. Predictors of ≥ 5% hip BMD loss at week 48 were P1NP increase [odds ratio (OR) 5.0; 95% confidence interval (CI) 1.1-27; P < 0.043]; N(t)RTI randomization (OR 6.7; 95% CI 2.0-27.1; P < 0.003), being African, higher baseline CD4 T cell count , and smoking. CONCLUSIONS: In a diverse cohort of viraemic HIV-infected patients, switching to second-line antiretroviral therapy (ART) was associated with clinically significant BMD loss, which was correlated with an early increase in P1NP. Measurement of P1NP may facilitate timely interventions to reduce rapid BMD loss among at-risk patients.

Comparison of calcaneal quantitative ultrasound and bone densitometry parameters as fracture risk predictors in type 2 diabetes mellitus.

AIM: To investigate the utility of calcaneal quantitative ultrasound compared with bone densitometry (DXA) in predicting incident low-trauma fracture in type 2 diabetes. METHODS: This retrospective cohort study included a subset of participants in the Dubbo Osteoporosis Epidemiology Study who had concurrent calcaneal quantitative ultrasound and DXA measurement, comprising 809 people without type 2 diabetes and 96 with type 2 diabetes. Fracture data had been collected prospectively. Cox proportional hazard models and receiver operating curves (ROC) were used to compare calcaneal quantitative ultrasound and DXA parameters as predictors for any low-trauma fracture. RESULTS: The median age of participants was 71 years (IQR 68-76, 50% men) for those without type 2 diabetes and 70 years (IQR 68-76, 55% men) for those with type 2 diabetes. There was no difference in low-trauma fracture incidence between groups when stratified by sex. In those without type 2 diabetes, the hazard ratio for fracture per 1 sd decrease in broadband ultrasound attenuation and femoral neck bone mineral density (BMD) was 1.47 [95% confidence interval (CI) 1.26-1.71] and 1.39 (95% CI 1.17-1.64), respectively. The corresponding figures in type 2 diabetes were 1.81 (95% CI 1.03-3.19) for broadband ultrasound attenuation and 2.55 (95% CI 1.28-5.08) for femoral neck BMD. CONCLUSION: Broadband ultrasound attenuation is comparable with femoral neck BMD as a predictor for low trauma incident fracture in type 2 diabetes. Calcaneal quantitative ultrasound offers several advantages over DXA and should be considered in further studies of bone health screening or in clinical practice where DXA is unavailable.

Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study.

Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival. INTRODUCTION: Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures. METHODS: The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables. RESULTS: Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73-2.42 in women and 2.49, 95% CI 2.00-3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21-1.84 and 1.81, 95% CI 1.37-2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52-2.35 and 1.77, 95% CI 1.16-2.71), respectively. CONCLUSION: Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention.

Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study.

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Vitamin D status and supplementation in adult patients receiving extracorporeal membrane oxygenation.

The prevalence of vitamin D deficiency in critical illness is known to be high and associated with adverse clinical outcomes. Patients receiving extracorporeal membrane oxygenation (ECMO) may be at increased risk of vitamin D deficiency due to high severity of acute illness. Challenges with drug dosing in ECMO patients are recognised due to increased volume of distribution and drug absorption to circuit components. To describe the prevalence of vitamin D deficiency in ECMO patients and the effect of intramuscular dosing of cholecalciferol on levels of vitamin D metabolites, and to compare these data with intensive care unit (ICU) patients not receiving ECMO, two prospective studies were performed sequentially: an observational study of 100 consecutive ICU patients and an interventional study assessing effects of intramuscular cholecalciferol in 50 ICU patients. The subgroup of patients who required ECMO support in each of these studies was analysed and compared to patients who did not receive ECMO. Twenty-four ECMO patients, 12 from the observational study and 12 from the interventional study (who received intramuscular cholecalciferol) were studied-21/24 (88%) ECMO patients were vitamin D deficient at baseline compared to 65/126 (52%) of non-ECMO patients (P=0.006). Of the 12 ECMO patients who received cholecalciferol, six patients (50%) achieved correction of deficiency compared to 36/38 (95%) non-ECMO patients (P=0.001). The prevalence of vitamin D deficiency is higher in ECMO patients compared to other critically ill adults. Correction of deficiency with single dose cholecalciferol is not reliable; higher or repeated doses should be considered to correct deficiency.

Osteoglycin, a novel coordinator of bone and glucose homeostasis.

OBJECTIVE: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. METHODS: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. RESULTS: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. CONCLUSIONS: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

Complex interplay among adiposity, insulin resistance and bone health.

Obesity and osteoporosis are common public health problems. Paradoxically, while obesity is associated with higher bone density, type 2 diabetic obese individuals have an increased fracture risk. Although obesity and insulin resistance co-exist, some obese individuals remain insulin-sensitive. We suggest that the apparent paradox relating obesity, bone density and fracture risk in type 2 diabetes may be at least partly influenced by differences in bone strength and quality between insulin-resistant and insulin-sensitive obese individuals. In this review, we focus on the complex interplay between, adiposity, insulin resistance and osteoporotic fracture risk and suggest that this is an important area of study that has implications for individually tailored and targeted treatment to prevent osteoporotic fracture in obese type 2 diabetic individuals.

Worsening of soft tissue dystrophic calcification in an osteoporotic patient treated with teriparatide.

Teriparatide, used for treatment of osteoporosis in patients at high risk of fracture risk, sometimes results in mild and transient hypercalcemia. There have been two recent reports of worsening dystrophic calcification in patients with autoimmune disorders following teriparatide treatment. We report a patient with severe osteoporosis and without a pre-existing autoimmune disorder, who developed symptomatic worsening of dystrophic calcification 4 months after teriparatide was initiated. Symptoms resolved within 1 week of teriparatide cessation.

More-than-minimal-trauma fractures are associated with low bone density: an 8-year prospective study.

Few studies have examined the relationship between more-than-minimal-trauma fractures and bone density. This study demonstrated that more-than-minimal-trauma fractures are associated with lower bone density similar to that seen in minimal trauma fractures. Men and women over 50 years with a more-than-minimal-trauma fracture should be investigated to exclude low bone density. INTRODUCTION: The aim of this study was to assess the prevalence and predictors of low bone density in men and women with more-than-minimal-trauma fractures. METHODS: In an Australian hospital, 630 community-dwelling men and women, 20 years of age or older, sustained a fracture due to more-than-minimal-trauma (force greater than a fall from standing height but less than high trauma). We studied 349 individuals who agreed to have a bone mineral density (BMD) scan. These participants were compared with 472 men and women with minimal trauma fractures. RESULTS: Men and women with more-than-minimal-trauma fractures had significantly lower bone density than expected for their age, gender and weight (Z-scorespine = -0.4 SD, 95 % confidence interval (CI), -0.5 to -0.3; Z-scorehip = -0.5 SD, 95 % CI, -0.6 to -0.4). Almost 1 in 4 of those over 50 years of age had osteoporosis by BMD criteria. The independent predictors of low bone density (T-score <-2.0 SD) were age equal to or over 50 years (odds ratio (OR) = 5.97, 95 % CI, 3.34 to 10.65), low body weight <20 kg/m2 (OR = 3.44, 95 % CI, 1.32 to 8.94), a prior minimal trauma fracture (OR = 2.76, 95 % CI, 1.17-6.52) and in those over 50 years of age, an osteoporosis-associated condition (OR = 4.51, 95 % CI, 1.69 to 12.06). Men and women with more-than-minimal-trauma fractures had similar bone density (Z-score) compared to those with minimal trauma fractures. CONCLUSIONS: Men and women over 50 years with a more-than-minimal-trauma fracture, especially those with low body weight, prior minimal trauma fracture or an osteoporosis-associated condition, should be investigated to exclude low bone density and its associated risk of subsequent fractures.

Association between fat mass, lean mass, and bone loss: the Dubbo Osteoporosis Epidemiology Study.

UNLABELLED: Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender. INTRODUCTION: Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year). METHODS: The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older were studied. RESULTS: Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P < 0.01). In bivariable regression analysis, each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower bone loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women. CONCLUSION: Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

Accelerated bone loss and increased post-fracture mortality in elderly women and men.

UNLABELLED: Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We found accelerated bone loss (≥1.31 % bone loss/year for women and ≥1.35 % bone loss/year for men) associated with 44-77 % increased mortality. It remains unclear whether bone loss is a marker or plays a role in mortality. INTRODUCTION: Osteoporotic fractures are associated with increased mortality although the cause is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated with increased mortality, but its role in mortality risk post-fracture is unclear. This study aimed to examine post-fracture mortality risk according to levels of bone loss. METHODS: Community-dwelling participants aged 60+ from Dubbo Osteoporosis Epidemiology Study with incident fractures were followed from 1989 to 2011. Kaplan-Meier survival curves were constructed according to bone loss quartiles. Cox proportional hazard models were used to determine the effect of bone loss on mortality. RESULTS: There were 341 women and 106 men with ≥2 BMD measurements. The rate of bone loss was similar for women and men (women mean -0.79 %/year, highest bone loss quartile -1.31 %/year; men mean -0.74 %/year, highest quartile -1.35 %/year). Survival was lowest for the highest quartile of bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture type, the association of bone loss with mortality was observed for vertebral (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an additional role in mortality risk following hip fractures. Importantly, overall, rapid bone loss was associated with 44-77 % increased mortality risk after multiple variable adjustment. CONCLUSION: Rapid bone loss was an independent predictor of post-fracture mortality risk in both women and men. The association of bone loss and post-fracture mortality was predominantly observed following vertebral fracture in both women and men and non-hip non-vertebral fracture in women. It remains to be determined whether bone loss is a marker or plays a role in the mortality associated with fractures.

Bone mineral density and association of osteoarthritis with fracture risk.

OBJECTIVE: High body mass index (BMI) is associated with increased risk of osteoarthritis (OA) and reduced risk of fragility fracture. However, the relationship between fragility fracture and OA remained unclear. This study sought to investigate the effect of bone mineral density (BMD) in the OA-fracture relationship. METHODS: Data from 2412 women and 1452 men aged >45 years in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Individuals have been followed for up to 22 years (median: 7.5 years; range: 0.1-22 years). Femoral neck BMD (FNBMD) and lumbar spine BMD (LSBMD) was measured by dual energy X-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). The presence of OA was ascertained at baseline by self-reported diagnosis. The incidence of low-trauma fracture was ascertained from X-ray reports. RESULTS: Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA (Hazard ratio (HR) = 1.50; 95% confidence interval (CI), 1.28-1.76). However, the association was mainly observed in women with osteopenic BMD (HR = 1.74; 95% CI, 1.38-2.17) and normal-BMD (HR = 1.50; 95% CI, 1.06-2.13) and not in those with osteoporosis. Further analysis revealed that osteopenic women with OA had significant increase in risk of vertebral (HR = 1.85; 95% CI, 1.24-2.75) and limb fracture (HR = 2.49; 95% CI, 1.77-3.48), but not in hip fracture. In men, no comparable relationship was found before and after adjustment for covariates. CONCLUSION: Women with OA have an increased risk of fragility fracture, and the risk was mainly observed in non-osteoporotic group.

Association between hypertension and fragility fracture: a longitudinal study.

UNLABELLED: Hypertension is an independent risk factor for osteoporosis and osteoporotic fracture in postmenopausal women. INTRODUCTION: Although hypertension has been suggested to be associated with increased fracture risk, it is not clear whether the association is independent of bone mineral density (BMD). The present study sought to examine the interrelationships between hypertension, BMD, and fracture risk. METHODS: The study included 1,032 men and 1,701 women aged 50 years and older who were participants in the Dubbo Osteoporosis Epidemiology Study. BMD at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp., Madison, WI, USA). The presence of hypertension was ascertained by direct interview and verification through clinical history. The incidence of fragility fractures was ascertained by X-ray report during the follow-up period (1989-2008). The Cox proportional hazards model was used to assess the association between hypertension and fracture risk. RESULTS: Women with hypertension had lower BMD at the femoral neck (0.79 versus 0.82 g/cm(2), P = 0.02) than those without the disease. After adjusting for BMD and covariates, hypertension was an independent risk factor for fragility fracture [hazard ratio (HR), 1.49; 95% CI, 1.13-1.96]. In men, hypertension was associated with higher femoral neck BMD (0.94 versus 0.92 g/cm(2), P = 0.02), but the association between hypertension and fracture risk did not reach statistical significance. CONCLUSION: Hypertension is associated with increased fracture risk in women, and the association is independent of BMD.

Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria.

UNLABELLED: This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in individuals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score > -2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD). INTRODUCTION: More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score > -2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in individuals with non-osteoporotic BMD. METHODS: We included 312 women and 390 men aged 62-90 years with BMD T-score > -2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011. RESULTS: Of the 702 participants, 26 % of women (n = 80/312) and 14 % of men (n = 53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR = 1.50; 95 % CI, 1.13-1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P = 0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment. CONCLUSION: These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD.