Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

Densitometer-Specific Differences in the Correlation Between Body Mass Index and Lumbar Spine Trabecular Bone Score.

Trabecular bone score (TBS) is a gray-level texture measure derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images that predicts fractures independent of bone mineral density (BMD). Increased abdominal soft tissue in individuals with elevated body mass index (BMI) absorbs more X-rays during image acquisition for BMD measurement and must be accommodated by the TBS algorithm. We aimed to determine if the relationship between BMI and TBS varied between 2 major manufacturers' densitometers, because different densitometers accommodate soft tissues differently. We identified 1919 women and 811 men, participants of the Canadian Multicentre Osteoporosis Study, aged ≥40 yr with lumbar spine DXA scans acquired on GE Lunar (4 centers) or Hologic (3 centers) densitometers at year 10 of follow-up. TBS was calculated for L1-L4 (TBS iNsight® software, version 2.1). A significant negative correlation between TBS and BMI was observed when TBS measurements were performed on Hologic densitometers in men (Pearson r = -0.36, p <0.0001) and in women (Pearson r = -0.33, p <0.0001); significant correlations were not seen when TBS was measured on GE Lunar densitometers (Pearson r = 0.00 in men, Pearson r = -0.02 in women). Age-adjusted linear regression models confirmed significant interactions between BMI and densitometer manufacturer for both men and women (p < 0.0001). In contrast, comparable positive correlations were observed between BMD and BMI on both Hologic and GE Lunar densitometers in men and women. In conclusion, BMI significantly affects TBS values in men and women when measured on Hologic but not GE Lunar densitometers. This finding has implications for clinical and research applications of TBS, especially when TBS is measured sequentially on DXA densitometers from different manufacturers or when results from different machines are pooled for analysis.

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.

Atypical Femoral Fractures: A Teaching Perspective.

This article provides an overview of atypical femoral fractures with a highlight on their radiographic findings. Potent antiresorptive agents such as bisphosphonates or denosumab have been associated with the development of such fractures. However, at this time, a causal association has not been conclusively established. Atypical femoral fractures are insufficiency fractures, which frequently present with bone pain. Early identification of characteristic radiographic features and withdrawal of antiresorptive therapy may prevent the development of completed atypical femoral fractures.

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men.

PURPOSE: To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data. METHODS: Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.

Choice of lumbar spine bone density reference database for fracture prediction in men and women: a population-based analysis.

The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (age- and BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60-0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women.

Sedentary behavior does not predict low BMD nor fracture-population-based Canadian Multicentre Osteoporosis Study.

Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1-L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture.

The number of hours of sitting in a day (often called "sedentary behavior") is currently understood to be "bad for bone health" both because of increased bone loss and a higher risk for fractures. Very few studies in randomly sampled men and women from a whole population have consistently asked about hours of sitting and examined baseline bone density. Fewer still have compared hours of sitting and its changes over 10 yr with changes in bone density and the number of new fractures that occurred. The Canadian Multicentre Osteoporosis Study obtained sitting hours from 5708 women and 2564 men aged 25 to 80+ yr and compared it with the spine, total hip (TH), and femoral neck (FN) bone density values. The average sitting at 7.4 h in men was associated with slightly lower adjusted femoral neck bone density; in women, sitting 6.7 h/d was associated with slightly lower adjusted FN and TH bone density. Ten-year follow-up data (now in about 5000 people) showed no relationship between the slightly longer sitting (an increase of 18% in men and 22% in women) and bone loss or new bone fractures. In this large country-wide population-based study, hours of sitting each day were not associated with 10-yr BMD loss in women or men nor did sitting more associate with new bone fractures. These data are reassuring; women and men who walk regularly and have some moderate-vigorous physical activity each day, despite more sitting, do not seem to be at greater risk for osteoporosis.

The role of morning basal serum cortisol in assessment of hypothalamic pituitary-adrenal axis.

PURPOSE: The use of morning basal serum cortisol levels as an alternative to dynamic testing for assessment of hypothalamic-pituitary-adrenal (HPA) axis has previously been reported. The purpose of this study was to determine the lower and upper cutoff values that would obviate subsequent HPA axis testing. METHODS: A single-centre, retrospective study from a tertiary care endocrinology clinic was conducted, analyzing data from 106 adult individuals referred for HPA axis testing who had undergone a 0800-0900 morning basal serum cortisol test followed by a standard dose (250 µg) adrenocorticotropin (ACTH) stimulation test. The ability of morning basal serum cortisol values to predict post-ACTH 30 or 60 minute peak cortisol value of >500 or >550 nmol/L was investigated. RESULTS: A morning basal cutoff of <128 nmol/L is sufficient for predicting a post-ACTH value<550 nmol/L, and morning basal cutoff levels of >243 nmol/L and >266 nmol/L predict peak post-ACTH values of >500 and >550 nmol/L respectively, obviating the need for dynamic testing. Regression analysis further demonstrated the log-linear relationship between morning basal and peak levels, while also finding a significant decrease in peak post-ACTH levels for patients diagnosed with secondary hypothyroidism (76 nmol/L lower, p=0.003) or secondary hypogonadism (61 nmol/L lower, p=0.02). These data suggest that the risk of cortisol deficiency is significantly higher in individuals with additional pituitary insufficiencies. The odds ratios for cortisol deficiency in patients with history of isolated secondary hypothyroidism was 3.41 (p=0.015), with isolated secondary hypogonadism was 4.77 (p=0.002) and with both was 7.45 (p=0.0002). CONCLUSION: Morning basal serum cortisol levels show promise as an effective screening test for HPA insufficiency for most patients. Clinicians should consider the high probability of HPA insufficiency in patients with one or more pituitary insufficiencies.

The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos).

OBJECTIVES: Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk. METHODS: We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years. RESULTS: In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up. CONCLUSIONS: PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX(®): a population-based report from CAMOS.

The WHO fracture risk assessment tool (FRAX(®)) estimates an individual's 10-yr major osteoporotic and hip fracture probabilities. When bone mineral density (BMD) is included in the FRAX calculation, only the femoral neck measurement can be used. Recently, a procedure was reported for adjusting major osteoporotic fracture probability from FRAX with femoral neck BMD based on the difference (offset) between the lumbar spine and the femoral neck T-score values. The objective of the current analysis was to independently evaluate this algorithm in a population-based cohort of 4575 women and 1813 men aged 50 yr and older from the Canadian Multicentre Osteoporosis Study. For women and men combined, there was a 15% (95% confidence interval 7-24%) increase in major osteoporotic fracture risk for each offset T-score after adjusting for FRAX probability calculated with femoral neck BMD. The effect was stronger in women than men, but a significant sex interaction was not detected. Among the full cohort, 5.5% had their risk category reclassified after using the offset adjustment. Sex- and age-dependent offsets (equivalent to an offset based on Z-scores) showed improved risk classification among individuals designated to be at moderate risk with the conventional FRAX probability measurement. In summary, the T-score difference between the lumbar spine and femoral neck is an independent risk factor for major osteoporotic fractures that is independent of the FRAX probability calculated with femoral neck BMD.

Current and Future Anti-VEGF Agents for Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the most common cause of legal blindness in developed countries. Neovascular (ie, wet) AMD is currently managed with intravitreal therapy. Traditional treatments (ie, bevacizumab, ranibizumab, aflibercept) provide high-efficacy therapy but can also require frequent dosing. Newer and future anti-VEGF therapies aim to decrease injection frequency through eitherlonger half life or port-delivery systems (brolucizumab, conbercept, KSI-301, ranibizumab). This review outlines current anti-VEGF treatments and ways by which their duration might be extended.

A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly.

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. © 2020 American Society for Bone and Mineral Research.

Vertebral Fractures in Individuals With Type 2 Diabetes: More Than Skeletal Complications Alone.

OBJECTIVE: We aimed to assess whether individuals with type 2 diabetes (T2D) have increased risk of vertebral fractures (VFs) and to estimate nonvertebral fracture and mortality risk among individuals with both prevalent T2D and VFs. RESEARCH DESIGN AND METHODS: A systematic PubMed search was performed to identify studies that investigated the relationship between T2D and VFs. Cohorts providing individual participant data (IPD) were also included. Estimates from published summary data and IPD cohorts were pooled in a random-effects meta-analysis. Multivariate Cox regression models were used to estimate nonvertebral fracture and mortality risk among individuals with T2D and VFs. RESULTS: Across 15 studies comprising 852,705 men and women, individuals with T2D had lower risk of prevalent (odds ratio [OR] 0.84 [95% CI 0.74-0.95]; I 2 = 0.0%; P het = 0.54) but increased risk of incident VFs (OR 1.35 [95% CI 1.27-1.44]; I 2 = 0.6%; P het = 0.43). In the IPD cohorts (N = 19,820), risk of nonvertebral fractures was higher in those with both T2D and VFs compared with those without T2D or VFs (hazard ratio [HR] 2.42 [95% CI 1.86-3.15]) or with VFs (HR 1.73 [95% CI 1.32-2.27]) or T2D (HR 1.94 [95% CI 1.46-2.59]) alone. Individuals with both T2D and VFs had increased mortality compared with individuals without T2D and VFs (HR 2.11 [95% CI 1.72-2.59]) or with VFs alone (HR 1.84 [95% CI 1.49-2.28]) and borderline increased compared with individuals with T2D alone (HR 1.23 [95% CI 0.99-1.52]). CONCLUSIONS: Based on our findings, individuals with T2D should be systematically assessed for presence of VFs, and, as in individuals without T2D, their presence constitutes an indication to start osteoporosis treatment for the prevention of future fractures.

Primary versus Tertiary Care Follow-Up of Low-Risk Differentiated Thyroid Cancer: Real-World Comparison of Outcomes and Costs for Patients and Health Care Systems.

BACKGROUND: An unprecedented rise in the prevalence of low-risk well-differentiated thyroid cancer (TC) has been reported in several countries, which is partly due to an increased utility of sensitive imaging techniques. The outcome of these cancers has generally remained excellent and the overall 5-year survival is almost 100%. However, the extended follow-up strategy for these patients remains unclear and while the initial management is done in specialist centres some experts opt to follow them on a long-term basis while others discharge them to primary care after the initial management. The effectiveness of one strategy versus the other has not been studied. METHODS: We conducted a real-world comparison to assess the outcome of low-risk TC (AJCC stage I) with undetectable thyroglobulin (TG) 2 years after radio-iodine (I-131) therapy. The outcome from Halifax (NS, Canada) and London (ON, Canada), where all TC patients are routinely followed by the tertiary care team, was compared with that from Edmonton (AB, Canada), where patients are routinely discharged to primary care. RESULTS: All patients were diagnosed between January 1, 2006, and December 31, 2011. The mean follow-up in primary care after discharge was 62.2 months and in tertiary care it was 64.6 months (p = 0.43). Rates of recurrence were similar in both groups, i.e., 1.1% in primary care and 1.3% in tertiary care (p = 0.69). Ultrasound surveillance was conducted in 56.5% of the patients in primary care and 52.6% of the tertiary care group (p = 0.26). The rate of annual unstimulated TG testing per patient was 0.58 (range 0-14) in primary care and 0.96 (range 0-6) in tertiary care (p = 0.06). More patients in primary care (86%) than in tertiary care (29.9%) consistently had thyroid-stimulating hormone levels within the target range (p < 0.001). The mean healthcare cost, based on a single follow-up visit with a blood test and ultrasound in the primary care group was CAD 118.01 and in the tertiary care group it was CAD 164.12. CONCLUSION: Our study shows that extended follow-up of low-risk TC patients is perfectly feasible in primary care and provides significant economic benefit for the healthcare system.

Parity and lactation are not associated with incident fragility fractures or radiographic vertebral fractures over 16 years of follow-up: Canadian Multicentre Osteoporosis Study (CaMos).

Parity and lactation showed no associations with incident clinical fragility fractures or radiographic vertebral compression fractures in the 16-year CaMos prospective study. Parity was associated with slightly greater decline in femoral neck but not hip or spine areal bone mineral density (aBMD), while lactation showed no associations with aBMD change. PURPOSE: Pregnancy and especially lactation cause loss of bone mass and microarchitectural changes, which temporarily increase fracture risk. After weaning, aBMD increases but skeletal microarchitecture may be incompletely restored. Most retrospective clinical studies found neutral or even protective associations of parity and lactation with fragility fractures, but prospective data are sparse. CaMos is a randomly selected observational cohort that includes ~ 6500 women followed prospectively for over 16 years. METHODS: We determined whether parity or lactation were related to incident clinical fragility fractures over 16 years, radiographic (morphometric and morphologic) vertebral fractures over 10 years, and aBMD change (spine, total hip, and femoral neck) over 10 years. Parity and lactation duration were analyzed as continuous variables in predicting these outcomes using univariate and multivariate regression analyses. RESULTS: Three thousand four hundred thirty-seven women completed 16 years of follow-up for incident clinical fractures, 3839 completed 10 years of morphometric vertebral fracture assessment, 3788 completed 10 years of morphologic vertebral fracture assessment, and 4464 completed 10 years of follow-up for change in aBMD. In the multivariate analyses, parity and lactation duration showed no associations with clinical fragility fractures, radiographic vertebral fractures, or change in aBMD, except that parity associated with a probable chance finding of a slightly greater decline in femoral neck aBMD. CONCLUSIONS: Parity and lactation have no adverse associations with clinical fragility or radiographic vertebral fractures, or the rate of BMD decline over 10 years, in this prospective, multicenter study of a randomly selected, population-based cohort of women.

Incident Fragility Fractures Have a Long-Term Negative Impact on Health-Related Quality of Life of Older People: The Canadian Multicentre Osteoporosis Study.

Although the short-term impact of incident fragility fractures on health-related quality of life (HRQL) of older people has been confirmed, we lack long-term evidence. We explored the impact of incident fragility fractures on HRQL, among people aged 50 years and older, using 10-year prospective data from the Canadian Multicentre Osteoporosis Study (CaMos). This study was based on data from 7753 (2187 men and 5566 women) participants of CaMos. The HRQL, measured through the Health Utility Index (HUI), was captured at baseline and year 10. The incident fragility fractures were recorded over 10 years of follow-up at spine, hip, rib, shoulder, pelvis, or forearm. Multivariable regression analysis was conducted to measure the mean difference, termed as deficit, in the HUI scores for participants with and without fractures. We examined the effects of single or multiple fragility fractures, time (fractures that occurred between year 1 to 5 and 6 to 10) and recovery to the prefracture level. Incident spine and hip fractures were associated with significant deficits (varied from -0.19 to -0.07) on the HUI scores. Hip and spine fractures were associated with negative impact on mobility, self-care, and ambulation. Fractures that occurred closer to the follow-up assessment were associated with significant impact on HRQL compared to fractures occurring a long time before it, except for hip fracture (deficits lasted 5 years or longer). Similarly, multiple hip (-0.14), spine (-0.16), and rib (-0.21) fractures significantly impacted the HRQL of women. Women with a hip fracture never recovered to their prefracture level score (OR = 0.41; 95% confidence interval [CI], 0.19 to 0.98). Our analysis suggests that single and multiple hip fractures as well as multiple spine and rib fractures strongly impact the HRQL of older people over a prolonged period of time. © 2019 American Society for Bone and Mineral Research.

Frailty and Risk of Fractures in Patients With Type 2 Diabetes.

OBJECTIVE: We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures. RESEARCH DESIGN AND METHODS: Data were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses. RESULTS: The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures. CONCLUSIONS: Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.

Predictors of imminent non-vertebral fracture in elderly women with osteoporosis, low bone mass, or a history of fracture, based on data from the population-based Canadian Multicentre Osteoporosis Study (CaMos).

Using data from the Canadian Multicentre Osteoporosis Study, several risk factors predictive of imminent (2-year) risk of low-trauma non-vertebral fracture among high-risk women were identified, including history of falls, history of low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to targeting this population for therapy. PURPOSE: Fracture risk assessment has focused on a long-term horizon and populations with a broad risk range. For elderly women with osteoporosis or low bone mass, or a history of fragility fractures ("high-risk women"), risk prediction over a shorter horizon may have greater clinical relevance. METHODS: A repeated-observations design and data from the Canadian Multicentre Osteoporosis Study were employed. Study population comprised women aged ≥ 65 years with T score (total hip, femoral neck, spine) ≤ - 1.0 or prior fracture. Hazard ratios (HR) for predictors of low-trauma non-vertebral fracture during 2-year follow-up were estimated using multivariable shared frailty model. RESULTS: The study population included 3228 women who contributed 5004 observations; 4.8% experienced low-trauma non-vertebral fracture during the 2-year follow-up. In bivariate analyses, important risk factors included age, back pain, history of falls, history of low-trauma fracture, physical function, health status, and total hip T score. In multivariable analyses, only four independent predictors were identified: falls in past 12 months (≥ 2 falls: HR = 1.9; 1 fall: HR = 1.5), low-trauma fracture in past 12 months (≥ 1 fracture: HR = 1.7), SF-36 physical component summary score (≤ 42.0: HR = 1.6), and total hip T score (≤ - 3.5: HR = 3.7; > - 3.5 to ≤ - 2.5: HR = 2.5; > - 2.5 to ≤ - 1: HR = 1.3). CONCLUSIONS: Imminent risk of low-trauma non-vertebral fracture is elevated among high-risk women with a history of falls or low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to identifying and targeting this population for therapy.