Associations of discordance in hip bone mineral density with hip osteoarthrosis severity and progression to total hip replacement in middle-aged adults.

The role of monitoring bone mineral density (BMD) as an indicator of an anti-fracture effect is controversial. Discordance between the spine and hip BMD is common and creates uncertainty in clinical practice. Using a population-based BMD Registry for the Province of Manitoba, Canada, we compared change in the spine and hip BMD as an indicator of treatment-related fracture risk reduction. The study cohort included 6093 women age >40years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7years). We computed change in the spine, total hip, and femur neck BMD between the first and second DXA scans as categorical (categorized as stable, detectable decrease, or detectable increase) and continuous measures. We modeled time to first incident fracture, ascertained from health services data, using Cox regression adjusted for baseline fracture probability. During a mean follow-up of 12.1years, 995 women developed incident major osteoporotic fractures (MOF) including 246 with hip fractures and 301 with clinical vertebral fractures. Women with a detectable decrease in total hip BMD compared with stable BMD experienced an increase in MOF (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.25-1.70) while those with a detectable increase in total hip BMD experienced a decrease in MOF (aHR 0.71, 95% CI 0.61-0.83), and these results were not attenuated when adjusted for change in spine BMD. Similar results were seen for hip and clinical vertebral fracture outcomes, when BMD change was assessed as a continuous measure, and when femur neck BMD monitoring was used instead of total hip BMD monitoring. Treatment-related increases in total hip BMD are associated with lower MOF, hip, and clinical vertebral fracture risk compared with stable BMD, while BMD decreases are associated with higher fracture risk. In contrast, spine BMD change is not independently associated with fracture risk.

The relationship between hormones and bone mineral density (BMD) in men has received considerable attention. However, most studies have been conducted in homogenous populations, and it is not known whether differences in hormones impact racial and ethnic differences in BMD. Our objective was to examine associations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) with BMD in a racially and ethnically diverse population. This was a population-based, observational survey. A total of 976 Black, Hispanic, and white randomly selected men ages 30-79 yr from the Boston Area Community Health/Bone Survey were included. BMD at the hip, wrist, and spine were calculated. The mean age of the sample was 46.7 +/- 12.4 yr. BMD levels were highest in black men, followed by Hispanic and then white men. Associations between hormones and BMD were consistent across racial and ethnic groups. Total and free testosterone was not correlated with BMD in age- or multivariate-adjusted models. SHBG was inversely correlated with total hip and ultradistal radius BMD after age adjustment, but not with multivariate adjustment for age, lean mass, fat mass, physical activity, self-rated health, and smoking. Total and free estradiol levels were positively and significantly correlated with femoral neck and total hip BMD, even with multivariate adjustment (partial correlations ranged between 0.11 and 0.16). However, estradiol levels failed to account for racial and ethnic differences in hip BMD. In our diverse population, neither serum total nor free testosterone levels were associated with BMD. Correlations between BMD and estradiol were significant but did not appear to account for any of the observed racial and ethnic differences in BMD. These findings suggest that differences in hormone levels are not a major contributor to the observed differences in BMD between Black, Hispanic, and white men.

There is a paucity of normative bone mineral density (BMD) data in healthy African women. Baseline total hip and lumbar spine BMD was measured in premenopausal women. BMD distribution was comparable to that of a reference population and was impacted by several factors including contraception and duration of lactation. Normative data on bone mineral density (BMD) and the cumulative impact of lactation, contraceptive use, and other factors on BMD in healthy African women have not been well studied. The objective of this study was to determine the factors associated with BMD in healthy premenopausal women in Uganda and Zimbabwe. Baseline total hip (TH) and lumbar spine (LS) BMD was measured by dual x-ray absorptiometry in 518 healthy, premenopausal black women enrolling in VOICE, an HIV-1 chemoprevention trial, at sites in Uganda and Zimbabwe. Contraceptive and lactation histories, physical activity assessment, calcium intake, and serum vitamin D levels were assessed. Independent factors associated with BMD were identified using an analysis of covariance model. The study enrolled 331 women from Zimbabwe and 187 women from Uganda. Median age was 29 years (IQR 25, 32) and median body mass index (BMI) was 24.8 kg/m(2) (IQR 22.2, 28.6). In univariate analyses, lower TH BMD values were associated with residence in Uganda (p < 0.001), lower BMI (p < 0.001), and any use of and duration of depot-medroxyprogresterone acetate. Use of oral contraceptives, progestin-only implants, and higher physical activity levels were protective against reduced BMD. Similarly, lower LS BMD values were associated with these same factors but also higher parity and history of breastfeeding. In a multivariable analysis, lower TH and LS BMD values were associated with enrollment in Uganda, lower BMI, and lower physical activity level; contraceptive use was associated with lower spine BMD, and breastfeeding contributed to lower total hip BMD. Among healthy premenopausal women, TH and LS BMD was higher in Zimbabwe than Uganda. Additional factors independently associated with BMD included BMI, physical activity level, contraceptive use, and lactation.

Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.

Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research.

AB0788 Predictors of Fractures in Excessive Consumption of Alcohol: An Observational Study

SummaryTo explore differences in bone mineral density (BMD) between dominant and non-dominant hip within levels of sport impact. BMD was higher in the non-dominant hip in high-impact sports, whereas the dominant hip had increased BMD for low-impact sports. The side-to-side differences were relatively small and not clinically relevant.PurposeIt is unknown whether there is difference in BMD at the hip between dominant and non-dominant sides in young athletes. The aims of this study were to explore the dominant–non-dominant differences in hip BMD in young athletes participating in low- and high-impact sports and to assess the effect of ground force impact on BMD.MethodsData was collected on University of Oxford athletes and controls (CG) between 2016 and 2018. Athletes were classified into two groups: high-impact sports (HIG) and low-impact sports (LIG). Total and regional measurements of both hips’ BMD were recorded using a dual-energy X-ray absorptiometry (DXA). Linear regression method was used to assess differences in BMD between and within groups.ResultsOne hundred ninety-four athletes (HIG: n = 89, LIG: n = 105) and 48 controls were included in this study. Total hip and femoral neck BMD was higher in athletes compared to the CG (p < 0.01), with HIG recording highest levels of BMD. The BMD difference between the dominant and non-dominant sides was significant in the LIG, with BMD being higher in the dominant side. Conversly, BMD was higher in the non-dominant hip within the HIG. However, the hip asymmetries were not clinically relevant (%BMD difference < 3%). A significant interaction between side and sport group on BMD was observed.ConclusionsHigh-impact sports had significantly higher BMD compared with low-impact sports and CG. BMD in the dominant hip was significantly higher for the LIG and lower in the HIG; however, differences were not clinically relevant.

Despite high bone mineral density (BMD), persons with type 2 diabetes are at greater risk of fracture. The relationship between body composition and BMD in noninsulin-requiring diabetes is unclear. The aim was to examine how fat and lean mass independently affect the skeleton in this population. Subjects for this cross-sectional analysis were men (n = 78) and women (n = 56) aged 40-65 years (56 ± 6 years) with uncomplicated, noninsulin-requiring type 2 diabetes. Total body fat and lean mass, total body, hip and lumbar spine BMD were measured with dual energy X-ray absorptiometry. Magnetic resonance imaging measured total abdominal, visceral and subcutaneous (SQ) fat. Subjects had normal all-site BMD and were obese to overweight (body mass index 29-41 kg/m(2)) with controlled diabetes (HbA1c women 6·6 ± 1·2%, men 6·7 ± 1·6%). Lean mass was positively associated with total body, hip, femoral neck and hip BMD in both sexes. Fat mass, abdominal total and SQ fat were associated with total body and hip BMD in women. In multivariate analyses adjusted for sex, lean mass significantly predicted total, hip and femoral neck BMD in men and women. In unadjusted models, lean mass continued to predict BMD at these sites in men; fat mass also predicted total body, femoral and hip BMD in women. In men and women with uncomplicated, noninsulin-requiring diabetes, lean mass significantly predicted BMD at the total body, hip and femoral neck. Further research is needed to determine whether acquisition or maintenance of lean mass in T2DM can prevent hip fracture in this at-risk population.

Management of diabetes-related foot ulceration (DFU) includes pressure offloading resulting in a period of reduced activity. The metabolic effects of this are unknown. This study aims to investigate changes in bone mineral density (BMD) and body composition 12 weeks after hospitalisation for DFU. A longitudinal, prospective, observational study of 22 people hospitalised for DFU was conducted. Total body, lumbar spine, hip and forearm BMD, and total lean and fat mass were measured by dual-energy X-ray absorptiometry (DXA) during and 12 weeks after hospitalisation for DFU. Significant losses in total hip BMD of the ipsilateral limb (− 1.7%, p < 0.001), total hip BMD of the contralateral limb (− 1.4%, p = 0.005), femoral neck BMD of the ipsilateral limb (− 2.8%, p < 0.001) and femoral neck BMD of the contralateral limb (− 2.2%, p = 0.008) were observed after 12 weeks. Lumbar spine and forearm BMD were unchanged. HbA1c improved from 75 mmol/mol (9.2%) to 64 mmol/mol (8.0%) (p = 0.002). No significant changes to lean and fat mass were demonstrated. Total hip and femoral neck BMD decreased bilaterally 12 weeks after hospitalisation for DFU. Future research is required to confirm the persistence and clinical implications of these losses.

Weight loss is associated with reduction in bone mineral density (BMD). The objective was to address the role of changes in fat mass (FM) and lean mass (LM) in BMD decline in both sexes. A 2-year randomized controlled trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS-LOST). The setting was the general community. Enrolled were 424 overweight and obese participants (mean age, 52 ± 9 y; 57% females). Intervention included weight loss diets differing in fat, protein, and carbohydrates. Main outcome measures were change in spine, total hip (TH), and femoral neck (FN) BMD and sex differences after dietary intervention. At baseline, a stronger correlation between BMD and body composition measurements was observed in women, primarily with LM (r = 0.419, 0.507, and 0.523 for spine, FN, and TH, respectively; all P < .001). In men, only LM correlated with hip BMD (r = 0.298; P < .001). Mean weight loss at 2 years was -6.9%, without differences among diets. Two-year changes in BMD were 0.005 (P = .04), -0.014 (P < .001), and -0.014 g/cm(2) (P < .001), at the spine, TH, and FN, respectively. These changes directly correlated with changes in LM in women (r = 0.200, 0.324, and 0.260 for spine, FN, and TH, respectively), whereas FM loss correlated only with changes in TH BMD (0.274; P < .001). In men, changes in LM (-0.323; P < .001) and FM (-0.213; P = .027) negatively correlated with changes in spine BMD. Weight loss diets result in sex-specific effects on BMD. Although men exhibited a paradoxical increase in spine BMD, women tended to decrease in BMD at all sites.

Association between bone mineral density and knee osteoarthritis in Koreans: the Fourth and Fifth Korea National Health and Nutrition Examination Surveys

Loss of estrogen results in a decrease in bone mineral density (BMD) and content (BMC) and an increase in cytokine production. Elevated cytokines lead to an upregulation of osteoclastogenesis. We determined the relationship between cytokines and BMD and BMC in healthy, postmenopausal women (n=105) not on hormone therapy. Spine BMD and BMC (SpBMD, SpBMC) and hip BMD and BMC were measured by dual energy x‐ray absorptiomety. We stimulated whole blood with three concentrations of lipopolysaccharide (low [L], medium [M], high [H]) and assessed cytokine production by a human cytokine multiplex immunoassay (LINCO research). Cytokine data were transformed. We observed significant associations between SpBMD and interleukin (IL)‐1M (p&lt;0.05) and IL‐1H (p&lt;0.01) plus SpBMC and IL‐1M (p=0.01), granulocyte‐colony stimulating factor (G‐CSF)M, IL‐6M, and IL‐1H (p&lt;0.05). Femoral neck (FN) BMC was significantly related to IL‐1M, interferon gamma (INFγ)M, IL‐7H, IL‐8H, and IL‐1H (p&lt;0.05) while total hip (TH) BMD was significantly associated with IL‐1M (p&lt;0.05). Stepwise multiple regression models were: SpBMD=0.651 + 0.00007(IL‐1H) + 0.005(age) SpBMC=32.869 ‐ 1.982(BMI) + 0.633(WT) + 0.459(age) + 0.377(IL‐1M) FN BMC=0.637 + 0.029(HT) + 0.0001(IL‐1H) ‐ 0.509(IL‐8H) + 0.212(IL‐7H) TH BMD=0.728 + 0.002(WT) + 0.003(IL‐1M) We confirmed that cytokine concentrations were related to SpBMC, SpBMD, FN BMC and TH BMD, but not to BMD or BMC at other sites, suggesting that cytokines mainly affect trabecular bone. Supported by funds from NIAMS/NIH (AR046922) and USDA/ARS,WHNRC.

The bone-specific physical activity questionnaire (BPAQ) accounts for activities that affect bone but has not been used in studies with older adults. Relationships exist between the BPAQ-derived physical activity and bone density in healthy middle-aged and older men but not men with prostate cancer. Disease-related treatments detrimental to bone should be considered when administering the BPAQ. The bone-specific physical activity questionnaire (BPAQ) was developed to account for bone-specific loading. In this retrospective study, we examined the relationship between BPAQ-derived physical activity and bone mineral density (BMD) in middle-aged and older men with and without prostate cancer. Two groups, 36 healthy men and 69 men with prostate cancer receiving androgen suppression therapy (AST), completed the BPAQ and had whole body, total hip, femoral (FN) and lumbar spine BMD assessed by dual-energy X-ray absorptiometry. Past (pBPAQ), current (cBPAQ) and total BPAQ (tBPAQ) scores for the healthy men were related to FN BMD (pBPAQ r = 0.36, p = 0.030; cBPAQ r s = 0.35, p = 0.034; tBPAQ r = 0.41, p = 0.014), and pBPAQ and tBPAQ were related to total hip (r s = 0.35, p = 0.035 and r s = 0.36, p = 0.029, respectively) and whole body BMD (r s = 0.44, p = 0.007 and r s = 0.45, p = 0.006, respectively). In men with prostate cancer, the BPAQ was not significantly associated with BMD. In stepwise regression analyses, body mass and tBPAQ predicted 30 % of the variance in total hip BMD (p = 0.003), cBPAQ predicted 14 % of the variance in FN BMD (p = 0.002), and body mass, age and tBPAQ predicted 47% of the variance in whole body BMD (p < 0.001) in healthy men. In men with prostate cancer, the BPAQ was not an independent predictor of BMD. Although BPAQ-derived estimates of physical activity are related to bone status in healthy middle-aged and older men, the adverse effect of AST on bone appears to obscure this relationship in men with prostate cancer.

In nine industrialized countries in North America, Europe, Japan, and Australia, country-specific osteoporosis prevalence (estimated from published data) at the total hip or hip/spine ranged from 9 to 38% for women and 1 to 8% for men. In these countries, osteoporosis affects up to 49 million individuals. Standardized country-specific prevalence estimates are scarce, limiting our ability to anticipate the potential global impact of osteoporosis. This study estimated the prevalence of osteoporosis in several industrialized countries (USA, Canada, five European countries, Australia, and Japan) using the World Health Organization (WHO) bone mineral density (BMD)-based definition of osteoporosis: BMD T-score assessed by dual-energy x-ray absorptiometry ≤-2.5. Osteoporosis prevalence was estimated for males and females aged 50years and above using total hip BMD and then either total hip or spine BMD. We compiled published location-specific data, using the National Health and Nutrition Examination Survey (NHANES) III age and BMD reference groups, and adjusted for differences in disease definitions across sources. Relevant NHANES III ratios (e.g., male to female osteoporosis at the total hip) were applied where data were missing for countries outside the USA. Data were extrapolated from geographically similar countries as needed. Population counts for 2010 were used to estimate the number of individuals with osteoporosis in each country. For females, osteoporosis prevalence ranged from 9% (UK) to 15% (France and Germany) based on total hip BMD and from 16% (USA) to 38% (Japan) when spine BMD data were included. For males, prevalence ranged from 1% (UK) to 4% (Japan) based on total hip BMD and from 3% (Canada) to 8% (France, Germany, Italy, and Spain) when spine BMD data were included. Up to 49 million individuals met the WHO osteoporosis criteria in a number of industrialized countries in North America, Europe, Japan, and Australia.

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than − 2. The mean lumbar spine Z score (− 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than − 2, respectively. The mean femoral neck (− 1.1 ± 1.1) and total hip (− 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = − 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.