Greater Bone Marrow Adiposity Predicts Bone Loss in Older Women

Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between ¹H-MRS–based measures of vertebral bone marrow adipose tissue (BMAT), annualized change in bone density/strength by quantitative computed tomography (QCT) and DXA, and secondarily, with incident clinical fractures and radiographic vertebral fractures among older adults. The associations between BMAT and annualized change in bone density/strength were evaluated using linear regression models, adjusted for age, body mass index (BMI), diabetes, estradiol, and testosterone. Cox proportional hazards models were used to evaluate the associations between baseline BMAT and incident clinical fractures, and logistic regression models for incident vertebral fractures. At baseline, mean ± SD age was 80.9 ± 4.2 and 82.6 ± 4.2 years in women (n = 148) and men (n = 150), respectively. Mean baseline BMAT was 55.4% ± 8.1% in women and 54.1% ± 8.2% in men. Incident clinical fractures occurred in 7.4% of women over 2.8 years and in 6.0% of men over 2.2 years. Incident vertebral fractures occurred in 12% of women over 3.3 years and in 17% of men over 2.7 years. Each 1 SD increase in baseline BMAT was associated with a 3.9 mg²/cm⁴/year greater loss of spine compressive strength index (p value = .003), a 0.9 mg/cm³/year greater loss of spine trabecular BMD (p value = .02), and a 1.2 mg/cm³/year greater loss of femoral neck trabecular BMD (p value = .02) in women. Among men, there were no associations between BMAT and changes in bone density/strength. There were no associations between BMAT and incident fractures in women or men. In conclusion, we found greater BMAT is associated with greater loss of trabecular bone at the spine and femoral neck, and greater loss of spine compressive strength, in older women. © 2019 American Society for Bone and Mineral Research.     

Sarcopenic Obesity and Its Temporal Associations With Changes in Bone Mineral Density,Incident Falls,and Fractures in Older Men: The Concord Health and Ageing in Men Project

Body composition and muscle function have important implications for falls and fractures in older adults. We aimed to investigate longitudinal associations between sarcopenic obesity and its components with bone mineral density (BMD) and incident falls and fractures in Australian community‐dwelling older men. A total of 1486 men aged ≥70 years from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2‐year follow‐up (2007–2009; n = 1238), and 5‐year follow‐up (2010–2013; n = 861). At all three time points, measurements included appendicular lean mass (ALM), body fat percentage and total hip BMD, hand‐grip strength, and gait speed. Participants were contacted every 4 months for 6.1 ± 2.1 years to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Sarcopenic obesity was defined using sarcopenia algorithms of the European Working Group on Sarcopenia (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) and total body fat ≥30% of total mass. Sarcopenic obese men did not have significantly different total hip BMD over 5 years compared with non‐sarcopenic non‐obese men (p > 0.05). EWGSOP‐defined sarcopenic obesity at baseline was associated with significantly higher 2‐year fall rates (incidence rate ratio [IRR] 1.66; 95% confidence interval [CI] 1.16–2.37), as were non‐sarcopenic obesity (1.30; 1.04–1.62) and sarcopenic non‐obesity (1.58; 1.14–2.17), compared with non‐sarcopenic non‐obese. No association with falls was found for sarcopenic obesity using the FNIH definition (1.01; 0.63–1.60), but after multivariable adjustment, the FNIH‐defined non‐sarcopenic obese group had a reduced hazard for any 6‐year fracture compared with sarcopenic obese men (hazard ratio 0.44; 95% CI 0.23–0.86). In older men, EWGSOP‐defined sarcopenic obesity is associated with increased fall rates over 2 years, and FNIH‐defined sarcopenic obese men have increased fracture risk over 6 years compared with non‐sarcopenic obese men. © 2016 American Society for Bone and Mineral Research.     

Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.     

Association of Serum Uric Acid and Incident Nonspine Fractures in Elderly Men: The Osteoporotic Fractures in Men (MrOS) Study

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case‐cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case‐cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case‐cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71–0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49–0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD. © 2014 American Society for Bone and Mineral Research.     

Physical Performance and Radiographic and Clinical Vertebral Fractures in Older Men

In men, the association between poor physical performance and likelihood of incident vertebral fractures is unknown. Using data from the MrOS study (N = 5958), we describe the association between baseline physical performance (walking speed, grip strength, leg power, repeat chair stands, narrow walk [dynamic balance]) and incidence of radiographic and clinical vertebral fractures. At baseline and follow‐up an average of 4.6 years later, radiographic vertebral fractures were assessed using semiquantitative (SQ) scoring on lateral thoracic and lumbar radiographs. Logistic regression modeled the association between physical performance and incident radiographic vertebral fractures (change in SQ grade ≥1 from baseline to follow‐up). Every 4 months after baseline, participants self‐reported fractures; clinical vertebral fractures were confirmed by centralized radiologist review of the baseline study radiograph and community‐acquired spine images. Proportional hazards regression modeled the association between physical performance with incident clinical vertebral fractures. Multivariate models were adjusted for age, bone mineral density (BMD, by dual‐energy X‐ray absorptiometry [DXA]), clinical center, race, smoking, height, weight, history of falls, activity level, and comorbid medical conditions; physical performance was analyzed as quartiles. Of 4332 men with baseline and repeat radiographs, 192 (4.4%) had an incident radiographic vertebral fracture. With the exception of walking speed, poorer performance on repeat chair stands, leg power, narrow walk, and grip strength were each associated in a graded manner with an increased risk of incident radiographic vertebral fracture (p for trend across quartiles <0.001). In addition, men with performance in the worst quartile on three or more exams had an increased risk of radiographic fracture (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.33–2.45) compared with men with better performance on all exams. Clinical vertebral fracture (n =149 of 5813, 2.6%) was not consistently associated with physical performance. We conclude that poorer physical performance is associated with an increased risk of incident radiographic (but not clinical) vertebral fracture in older men. © 2014 American Society for Bone and Mineral Research.     

Progressive Temporal Change in Serum SHBG,But Not in Serum Testosterone or Estradiol,Is Associated With Bone Loss and Incident Fractures in Older Men: The Concord Health and Ageing in Men Project

This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non‐vertebral) over an average of 6 years of follow‐up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2‐year follow‐up (n = 1367), and 5‐year follow‐up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography–tandem mass spectrometry [LC‐MS/MS]), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) (by immunoassay) were measured at all time‐points, whereas free testosterone (cFT) was calculated using a well‐validated formula. Hip BMD was measured by dual‐energy X‐ray absorptiometry (DXA) at all three time‐points, and fracture data were verified radiographically. Statistical modeling was done using general estimating equations (GEEs). For total hip BMD, univariable analyses revealed inverse associations with temporal changes in serum SHBG, FSH, and LH and positive associations for serum E1 and cFT across the three time‐points. In models adjusted for multiple covariables, serum SHBG (β = –0.029), FSH (β = –0.065), LH (β = –0.049), E1 (β = 0.019), and cFT (β = 0.033) remained significantly associated with hip BMD. However for femoral neck BMD, only FSH (β = –0.048) and LH (β = –0.036) remained associated in multivariable‐adjusted models. Temporal change in serum SHBG, but not T, E2, or other hormonal variables, was significantly associated with any, nonvertebral or hip fracture incidence in univariable analyses. In multivariable‐adjusted models, temporal increase in serum SHBG over time remained associated with any fracture (β = 0.060) and hip fracture (β = 0.041) incidence, but not nonvertebral fracture incidence. These data indicate that a progressive increase in circulating SHBG over time predicts bone loss and fracture risk in older men. Further studies are warranted to further characterize changes in circulating SHBG as a mechanism and/or biomarker of bone health during male ageing. © 2016 American Society for Bone and Mineral Research.     

Bone Mineral Density Predicts Fractures in Chronic Kidney Disease

Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA), and/or high‐resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low‐trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm² (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm² (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm³ (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm³ (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD. © 2014 American Society for Bone and Mineral Research.     

Factors Associated With Kyphosis and Kyphosis Progression in Older Men: The MrOS Study

Hyperkyphosis (HK), or increased anterior curvature of the thoracic spine, is common in older persons. Although it is thought that vertebral fractures are the major cause of HK, only about a third of those with the worst degrees of kyphosis have underlying vertebral fractures. In older men, HK is associated with increased risk of poor physical function, injurious falls, and earlier mortality, but its causes are not well understood. We studied 1092 men from the Osteoporotic Fractures in Men (MrOS) Study aged 64 to 92 years (mean age 72.8 years) who had repeated standardized radiographic measures of Cobb angle of kyphosis to identify risk factors for HK (defined as ≥50 degrees) and kyphosis progression over an interval of 4.7 years. Specifically, we examined the associations with age, body mass index (BMI), weight, weight loss, health behaviors, family history of HK, muscle strength, degenerative disc disease (DDD), bone mineral density (BMD), prevalent thoracic vertebral fractures, and incident thoracic vertebral fractures (longitudinal analyses only). Men had an average baseline kyphosis of 38.9 (standard deviation [SD] 11.4) degrees. Fifteen percent had HK (n = 161) with a mean Cobb angle of 56.7 (SD = 6.0) degrees; these men were older (p < 0.01), had lower BMI (p < 0.01), lower BMD (p < 0.01), were more likely to have family history of HK (p = 0.01), and prevalent thoracic vertebral fracture (p < 0.01) compared with the men without HK. During follow-up, men experienced an average of 1.4 degrees of kyphosis progression with DDD (p = 0.04) and lower hip BMD (p < 0.01) being identified as statistically significant and incident vertebral fractures (p = 0.05) nearly significant factors associated with worse progression. These results suggest that in older men, HK results from not only low BMD and vertebral fractures but that DDD also may play a significant role in kyphosis progression. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Vitamin D Receptor Start Codon Polymorphism (Fok I) and Bone Mineral Density in Chinese Men and Women

The relationship between Fok I polymorphism of the vitamin D receptor start codon, bone mineral density (BMD) and vertebral fractures was studied in 684 Chinese men and women. A significant trend was observed only in Chinese women aged 70–79 years. The mean BMD at the total body was 0.85 ± 0.01 g/cm², 0.82 ± 0.01 g/cm²and 0.84 ± 0.01 g/cm² for elderly women of the FF, Ff and ff genotypes respectively (p= 0.06 by ANOVA). Similar but statistically non-significant trends were observed at the hip and spine. However, no association between BMD and the Fok I genotype was observed in younger women (aged 50–59 years) and elderly men (aged 70–79 years). In all study groups, there was no effect of an interaction between Fok I polymorphism and calcium intake on BMD (p>0.05 for the interaction effects by two-way ANOVA). No significant association was observed between Fok I polymorphism and vertebral fracture in elderly men or women (p>0.05 by the chi-square test). We conclude that the Fok I polymorphism may have a weak effect on the BMD of elderly Chinese women. Received: 2 February 2001 / Accepted: 27 August 2001     

Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation

 Organ transplantation is associated with a high turnover of bone metabolism, and an increased loss of bone mass and incidence of osteoporotic fractures. Established therapies for osteoporosis after organ transplantation are still lacking, however. We report on an intravenous bisphosphonate therapy initiated in transplant patients because of a high rate of bone loss or incident osteoporotic fractures. Twenty-one patients after liver transplantation and 13 patients after heart transplantation received 30 mg pamidronate intravenously every 3 months, combined with 1000 mg calcium and 1000 IU vitamin D per day. The median time interval between transplantation and start of pamidronate treatment was 1.9 years in cardiac patients and 2.3 years in liver patients. Lumbar spine bone mineral density (LS BMD) and femoral neck BMD (FN BMD) were measured before and every 6 months after pamidronate therapy was initiated. Spinal radiographs were performed annually. Biochemical markers of bone metabolism were determined every 3 months, immediately before pamidronate administration. From a previous observational study, 58 patients treated only with calcium and vitamin D were matched for age, sex, pretransplantation LS BMD and time interval between transplantation and the first pamidronate treatment. In the pamidronate-treated patients, the mean increase in LS BMD adjusted for baseline values amounted to 0.080 ± 0.038 g/cm² (8.6 ± 4.0 %) after 1 year and 0.091 ± 0.058 g/cm² (10.4 ± 6.1%) after 2 years compared with 0.001 ± 0.037 g/cm² (0.26 ± 4.0%) after 1 year and 0.015 ± 0.057 g/cm² (1.8 ± 6.0%) after 2 years in the historical control group (absolute LS BMD changes pamidronate group vs historical group p < 0.0001 after 1 and 2 years). The changes of FN BMD were 0.024 ± 0.043 g/cm² (3.2 ± 6.1%) after 1 year and 0.046 ± 0.052 g/cm² (7.0 ± 6.1%) after 2 years in the pamidronate group compared with −0.012 ± 0.043 g/cm² (−1.6 ± 6.1%) after 1 year and −0.013 ± 0.052 g/cm² (−1.1 ± 6.1%) after 2 years in the historical control group (absolute FN BMD changes pamidronate group vs historical group p=0.003 after 1 year and p=0.001 after 2 years). From a total of 287 application cycles of pamidronate treatment, no severe side effects were observed and non-severe side effects were seen in only 39 cycles (13.6%). We conclude that cyclic intravenous pamidronate treatment is beneficial to patients with low bone mass or osteoporotic fractures following transplant, even when not immediately initiated. Received: 5 March 2002 / Accepted: 27 August 2002     

Estimation of the Prevalence of Low Bone Density in Canadian Women and Men Using a Population-Specific DXA Reference Standard: The Canadian Multicentre Osteoporosis Study (CaMos)

The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 ± 0.121 g/cm² for women and 1.058 ± 0.127 g/cm² for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 ± 0.125 g/cm² for women and 0.910 ± 0.125 g/cm² for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%. Received: 23 April 1999 / Accepted: 14 April 2000     

Calcaneus Bone Mineral Density is Lower Among Men and Women with Lower Physical Performance

Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand, and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus BMD between people with and those without regular physical activity in both genders, and most differences were not significant. However, there were significant BMD increases of 3–6% per standard deviation (SD) increase in all performance measures for women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together, which would increase fracture risk more than either risk factor alone. Received: 9 August 1999 / Accepted: 4 February 2000     

Comparative Analysis of the Radiology of Osteoporotic Vertebral Fractures in Women and Men: Cross‐Sectional and Longitudinal Observations from the Canadian Multicentre Osteoporosis Study (CaMos)

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm‐based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X‐ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00–1.00] to 0.88 [0.76–1.00]) than by GSQ (ranging from 0.38 [0.17–0.60] to 0.69 [0.54–0.85]). GSQ VF prevalence (16.4% [95% CI 15.4–17.4]) and incidence (10.2/1000 person‐years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1–7.4] and incidence 6.3/1000 person‐years [5.5–7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid‐thoracic spine, whereas prevalent mABQ and incident VFs by both methods co‐localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L₁ to L₄ bone mineral density (BMD) (–0.065 g/cm² [–0.087 to –0.042]), femoral neck BMD (–0.051 g/cm² [–0.065 to –0.036]), and total hip BMD (–0.059 g/cm² [–0.076 to –0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2–5.0]), incident VF by mABQ (9.0 [5.3–15.3]), and incident non‐vertebral major osteoporotic fractures (1.9 [1.2–3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non‐vertebral major osteoporotic fractures (OR = 3.0 [1.4–6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments. © 2017 American Society for Bone and Mineral Research.     

Change in hip bone mineral density and risk of subsequent fractures in older men

Low bone mineral density (BMD) increases fracture risk; how changes in BMD influence fracture risk in older men is uncertain. BMD was assessed at two to three time points over 4.6 years using dual‐energy X‐ray absorptiometry (DXA) for 4470 men aged ≥65 years in the Osteoporotic Fractures in Men (MrOS) Study. Change in femoral neck BMD was estimated using mixed effects linear regression models. BMD change was categorized as “accelerated” (≤?0.034 g/cm²), “expected” (between 0 and ?0.034 g/cm²), or “maintained” (≥0 g/cm²). Fractures were adjudicated by central medical record review. Multivariate proportional hazards models estimated the risk of hip, nonspine/nonhip, and nonspine fracture over 4.5 years after the final BMD measure, during which time 371 (8.3%) men experienced at least one nonspine fracture, including 78 (1.7%) hip fractures. Men with accelerated femoral neck BMD loss had an increased risk of nonspine (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.4–2.8); nonspine/nonhip (HR = 1.6; 95% CI 1.1–2.3); and hip fracture (HR = 6.3; 95% CI 2.7–14.8) compared with men who maintained BMD over time. No difference in risk was seen for men with expected loss. Adjustment for the initial BMD measure did not alter the results. Adjustment for the final BMD measure attenuated the change in BMD‐nonspine fracture and the change in BMD‐nonspine/nonhip relationships such that they were no longer significant, whereas the change in the BMD‐hip fracture relationship was attenuated (HR = 2.6; 95% CI 1.1–6.4). Total hip BMD change produced similar results. Accelerated decrease in BMD is a strong, independent risk factor for hip and other nonspine fractures in men. © 2012 American Society for Bone and Mineral Research.     

Impact of smoking on bone mineral density and bone metabolism in elderly men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study

Summary

Our cross-sectional analysis of 1,576 men aged ??65?years examined smoking effects on bone status. Number of smoking years was associated with decreased bone mineral density (BMD), after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not affect biochemical marker serum values for bone turnover.

Introduction

The impact of smoking on bone status in men has not been conclusively established. We examined how smoking and its cessation influence bone status and metabolism in men.

Methods

We analyzed 1,576 men among a baseline survey of Japanese men aged ??65?years, the Fujiwara-kyo Osteoporosis Risk in Men study, conducted during 2007?C2008.

Results

Lumbar spine (LS) BMD values among never, former, and current smokers were 1.045?±?0.194, 1.030?±?0.189, and 1.001?±?0.182?g/cm² (P?=?0.005), respectively, while total hip (TH) BMD values were 0.888?±?0.120, 0.885?±?0.127, and 0.870?±?0.124 (P?=?0.078), respectively. The significant trend for LS BMD remained after adjusting for the covariates; age, height, weight, physical activity, milk consumption, and drinking habit (P?=?0.036). Among never and ever (current and former) smokers, LS and TH BMD decreased with the number of pack years or the number of smoking years, respectively, adjusted for those covariates. Among ever smokers, LS and TH BMD decreased with the number of smoking years after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not reveal significant effect for serum osteocalcin or tartrate resistant acid phosphatase isoenzyme 5b.

Conclusion

The impact of smoking on bone status is mainly associated with the number of smoking years in elderly men.     

Bone mineral density in chinese elderly women with hip fracture

In order to examine the status of osteoporosis of the patients with hip fracture, we assessed the bone mineral density (BMD) of the contralateral hip of 81 elderly females with hip fracture and compared those with 77 normal Chinese women. The age of fracture subjects was 73.5±6.6 years (mean±SD), and 69.2±6.9 years for the controls. All of these fractures were caused by minor trauma, such as falls from a standing position or slipping to the ground. The Norland 2600 dual-photon absorptiometer (DPA) was used to evaluated the BMD in the femoral neck, trochanter, and Ward's triangle areas. The BMD for the fracture subjects was significantly lower than those of the controls. By linear regression, the probability of fracture increased exponentially with age and low BMD. The mean BMD for femoral neck of the fracture subjects versus controls was 0.556 versus 0.624 g/cm²; for trochanter: 0.505 versus 0.566 g/cm²; for Ward's triangle: 0.432 versus 0.485 g/cm². Both negative predictive value (NPV) and positive predictive value (PPV) were acceptable at the prevalence of hip fracture of 5% or 20% and at a cutoff point of 0.65 g/cm². These data revealed that the degree of relative osteoporosis in the patients with hip fractures was more severe than that of controls.     

Association of Trabecular Bone Score (TBS) With Incident Clinical and Radiographic Vertebral Fractures Adjusted for Lumbar Spine BMD in Older Men: A Prospective Cohort Study

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual‐energy X‐ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow‐up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41‐fold (95% confidence interval [CI] 1.23 to 1.63) higher aged‐adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age‐adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m²; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI. © 2017 American Society for Bone and Mineral Research.     

Mild hyponatremia as a risk factor for fractures: The rotterdam study

Recent studies suggest that mild hyponatremia is associated with fractures, but prospective studies are lacking. We studied whether hyponatremia is associated with fractures, falls, and/or bone mineral density (BMD). A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospective population‐based Rotterdam Study. The following data were analyzed: BMD, vertebral fractures (mean follow‐up 6.4 years), nonvertebral fractures (7.4 years), recent falls, comorbidity, medication, and mortality. Hyponatremia was detected in 399 subjects (7.7%, 133.4 ± 2.0 mmol/L). Subjects with hyponatremia were older (73.5 ± 10.3 years versus 70.0 ± 9.0 years, p < .001), had more recent falls (23.8% versus16.4%, p < .01), higher type 2 diabetes mellitus prevalence (22.2% versus 10.3%, p < .001), and more often used diuretics (31.1% versus 15.0%, p < .001). Hyponatremia was not associated with lower BMD but was associated with increased risk of incident nonvertebral fractures [hazard ratio (HR) =1.39, 95% confidence interval (CI) 1.11–1.73, p = .004] after adjustment for age, sex, and body mass index. Further adjustments for disability index, use of diuretics, use of psycholeptics, recent falls, and diabetes did not modify results. In the fully adjusted model, subjects with hyponatremia also had increased risk of vertebral fractures at baseline [odds ratio (OR) = 1.78, 95% CI 1.04–3.06, p = .037] but not at follow‐up. Finally, all‐cause mortality was higher in subjects with hyponatremia (HR = 1.21, 95% CI 1.03–1.43, p = .022). It is concluded that mild hyponatremia in the elderly is associated with an increased risk of vertebral fractures and incident nonvertebral fractures but not with BMD. Increased fracture risk in hyponatremia also was independent of recent falls, pointing toward a possible effect on bone quality. © 2011 American Society for Bone and Mineral Research     

High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men

Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC‐MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow‐up of 9.1 years. In a subsample of these men (n = 2256), spine X‐rays were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.     

High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function: The MrOS Sweden Cohort

Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean ± SD EPO was 11.5 ± 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR ≥60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = −0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray–verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35–1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08–1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00–2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function. © 2019 American Society for Bone and Mineral Research.