Application of epidemiology to change health policy : defining age-related thresholds of bone mineral density for primary prevention of fracture

In Australia, benefits for antifracture therapies have been available for patients with osteoporosis and a prior fracture. No benefits were available to those with no prior fracture. We aimed to define, in women with no prior fracture, age-related thresholds of bone mineral density (BMD) associated with fracture risk equivalent to that of women with prior fracture and osteoporosis. A case-control study of women (≥50 yr) was conducted, including 291 fracture cases and 823 controls. BMD was measured at the proximal femur and posterior anterior (PA) spine. A fracture risk score (FRS) for the group with no prior fracture was calculated with discriminant analysis. The thresholds for equivalent fracture risk between those with no prior fracture and those with prior fracture were assessed using logistic regression. Increasing the FRS to +0.98 in women with no prior fracture resulted in equivalent odds of sustaining a fracture to those with prior fracture and osteoporosis. The corresponding T-score thresholds at the spine were −4.6 at 50 yr, −3.9 at 60 yr, −3.1 at 70 yr, and −2.4 at 80 yr. The femoral neck T-score thresholds were lower by 0.5 standard deviation. The high-risk individuals defined by this study should be considered for primary fracture prevention therapy.

Pregnancy and lactation have no long-term deleterious effect on measures of bone mineral in healthy women: a twin study

BACKGROUND: The long-term effects of pregnancy and lactation on measures of bone mineral in women remain unclear.

OBJECTIVE: We studied whether pregnancy or lactation has deleterious long-term effects on bone mineral in healthy women.

DESIGN: We measured bone mineral density (BMD; g/cm(2)) in women aged > or = 18 y. Analyses were performed on 3 data sets: study 1, 83 female twin pairs (21 monozygous and 62 dizygous) aged (x +/- SD) 42.2 +/- 15.5 y who were discordant for ever having been pregnant beyond 20 wk; study 2, 498 twin pairs aged 42.3 +/- 15.0 y; and study 3, 1354 individual twins, their siblings, and family members.

RESULTS: In study 1, there were no significant within-pair differences in unadjusted BMD or BMD adjusted for age, height, and fat mass at the lumbar spine or total-hip or in total-body bone mineral content (BMC; kg) (paired t tests). In study 2, there was no significant within-pair difference in measures of bone mineral or body composition related to the within-pair difference in number of pregnancies. In study 3, subjects with 1 or 2 (n = 455) and > or = 3 pregnancies (n = 473) had higher adjusted lumbar spine BMD (2.9% and 3.8%, respectively; P = 0.001) and total-body BMC (2.2% and 3.1%; P < 0.001) than did nulliparous women (n = 426). Parous women who breast-fed had higher adjusted total-body BMC (2.6%; P = 0.005), total-hip BMD (3.2%; P = 0.04), and lower fat mass (10.9%; P = 0.01) than did parous non-breast-feeders.

CONCLUSION: We found no long-term detrimental effect of pregnancy or breast-feeding on bone mineral measures.

Age does not influence the bone response to treadmill exercise in female rats

Purpose: Because it is believed that bone may respond to exercise differently at different ages, we compared bone responses in immature and mature rats after 12 wk of treadmill running.

Methods: Twenty-two immature (5-wk-old) and 21 mature (17-wk-old) female Sprague Dawley rats were randomized into a running (trained, N = 10 immature, 9 mature) or a control group (controls, N = 12 immature, 12 mature) before sacrifice 12 wk later. Rats ran on a treadmill five times per week for 60-70 min at speeds up to 26 m[middle dot]min-1. Both at baseline and after intervention, we measured total body, lumbar spine, and proximal femoral bone mineral, as well as total body soft tissue composition using dual-energy x-ray absorptiometry (DXA) in vivo. After sacrificing the animals, we measured dynamic and static histomorphometry and three-point bending strength of the tibia.

Results: Running training was associated with greater differences in tibial subperiosteal area, cortical cross-sectional area, peak load, stiffness, and moment of inertia in immature and mature rats (P < 0.05). The trained rats had greater periosteal bone formation rates (P < 0.01) than controls, but there was no difference in tibial trabecular bone histomorphometry. Similar running-related gains were seen in DXA lumbar spine area (P = 0.04) and bone mineral content (BMC;P = 0.03) at both ages. For total body bone area and BMC, the immature trained group increased significantly compared with controls (P < 0.05), whereas the mature trained group gained less than did controls (P < 0.01).

Conclusion: In this in vivo model, where a similar physical training program was performed by immature and mature female rats, we demonstrated that both age groups were sensitive to loading and that bone strength gains appeared to result more from changes in bone geometry than from improved material properties.

Depression and bone mineral density in a community sample of perimenopausal women: Geelong Osteoporosis Study

Objective: Reduced bone mineral density (BMD) in women with a history of depressive disorders has been shown in some, but not all studies. This study investigated the association between self-reported depression and BMD in an age-stratified community sample of perimenopausal women residing in the South-Eastern region of Australia.

Design: Symptoms of depression in the year between July 2000 and July 2001 were ascertained by a self-report questionnaire based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Women in the perimenopausal group who had undergone a BMD total hip and spine assessment within the 12-month period after the depression assessment were included in the analysis, resulting in a sample of 78 women aged 45 to 60 years.

Results: In this sample, 14 women were identified as depressed. There was no difference in age, hormone therapy (HT) use, or unadjusted BMD at the total hip or spine between the depressed and nondepressed women (P = 0.14, 0.89, 0.57, and 0.70, respectively), but the depressed women tended to be heavier [depressed (median weight, interquartile range = 80 kg, 66-94) vs nondepressed (72 kg, 61-80) P = 0.06]. Whereas there was no significant difference in age-, HT-, and weight-adjusted BMD at the spine [depressed (mean ± SE = 1.21 ± 0.05) vs nondepressed (1.28 ± 0.03 g/cm2) P = 0.18], adjusted BMD at the total hip for the depressed women was 7.8% lower than for the nondepressed [depressed (mean ± SE = 0.957 ± 0.038) vs nondepressed (1.038 ± 0.023 g/cm2) P = 0.04].

Conclusions: These results suggest that in perimenopausal women, self-reported depression is associated with lower BMD at the hip.

Depression and bone mineral density in a community sample of men : Geelong Osteoporosis Study

Background : Previous research in psychiatric and community samples has demonstrated reduced bone mineral density (BMD) in individuals with both clinical depression and depressive symptoms, although the findings are equivocal. This study aimed to investigate the association between self-reported depression and BMD in a community sample of men aged 20–96 years enrolled in the Geelong Osteoporosis Study.

Methods : A self-report questionnaire based on DSM-IV criteria was used to determine lifetime prevalence rates of depression within the study sample at baseline. Those currently taking oral glucocorticoids, testosterone or bisphosphonates were excluded from the analysis (n = 23) resulting in a sample of 1279 men.

Results : In this sample, 155 men reported a lifetime history of depression (LHX). There were no differences in age, weight, height, calcium intake, smoking rates or unadjusted BMD at the femoral neck between the cases and the controls, whereas unadjusted BMD at the spine was significantly lower in those with a LHX (1.254 ± 0.187 vs 1.293 ± 0.194 g/cm2). BMD adjusted for age, weight, calcium intake and smoking was 3.6% lower at the spine (1.255 ± 0.016 vs 1.295 ± 0.006 g/cm2) and 3.4% lower at the femoral neck (0.973 ± 0.011 vs 1.007 ± 0.004 g/cm2) in those with a LHX compared to controls.

Conclusion : These data are consistent with previous findings of diminished BMD in people with depressive disorders and symptoms and suggest that depression may be a risk factor for reduced BMD in community-dwelling adult men.

Bone mineral density and incidence of hip fracture in Swedish urban and rural women 1987–2002

Background and purpose Although the incidence of hip fracture during the past 50 years has increased, a break in this trend has been reported in the last decade. Whether this change is attributable to changes in bone mineral density (BMD) or whether it varies between urban and rural regions is unknown.

Methods We evaluated changes in annual hip fracture incidence in women aged ≥ 50 years in one urban population (n = 51,757) and one rural population (n = 26,446) from 1987 to 2002. We also examined secular differences in BMD (mg/cm2), evaluated by single-photon absorptiometry at the distal radius, prevalence of osteoporosis, and several other risk factors for hip fracture in one population-based sample of urban women and one sample of rural women aged 50–80 years at two time points: 1988/89 (n = 257 and n = 180, respectively) and 1998/99 (n = 171 and n = 118, respectively).

Results No statistically significant changes were evident in annual age-adjusted hip fracture incidence per 104 when analyzing all women (–0.01 per year (95% CI: –0.37, 0.35)), rural women (–0.38 per year (-1.05, 0.28)), or urban women (0.19 per year (–0.28, 0.67)). BMD (expressed as T-score) was similar in 1988/99 and 1998/99 when analyzing all women (–0.09 (–0.26, 0.09)), urban women (–0.04 (–0.27, 0.19)), or rural women (–0.15 (–0.42, 0.13)) women.

Interpretation Since no changes in age-adjusted hip fracture incidence and no differences in BMD were found during the study period, changes evident in the other risk factors for hip fracture that we investigated (such as gait velocity and balance) are either of minor importance or are counteracted by changes in other risk factors.

Direction-specific diaphyseal geometry and mineral mass distribution of tibia and fibula: A pQCT study of female athletes representing different exercise loading types

Bones adapt to prevalent loading, which comprises mainly forces caused by muscle contractions. Therefore, we hypothesized that similar associations would be observed between neuromuscular performance and rigidity of bones located in the same body segment. These associations were assessed among 221 premenopausal women representing athletes in high-impact, odd-impact, highmagnitude, repetitive low-impact, and repetitive nonimpact sports and physically active referents aged 17–40 years. The whole group mean age and body mass were 23 (5) and 63 (9) kg, respectively. Bone cross sections at the tibial and fibular mid-diaphysis were assessed with peripheral quantitative computed tomography (pQCT). Density-weighted polar section modulus (SSI) and minimal and maximal crosssectional moments of inertia (Imin, Imax) were analyzed. Bone morphology was described as the Imax/Imin ratio. Neuromuscular performance was assessed by maximal power during countermovement jump (CMJ). Tibial SSI was 31% higher in the high-impact, 19% in the odd-impact, and 30% in the repetitive low-impact groups compared with the reference group (P\0.005). Only the high-impact group differed from the referents in fibular SSI (17%, P\0.005). Tibial morphology differed between groups (P = 0.001), but fibular morphology did not (P = 0.247). The bone-bygroup interaction was highly significant (P\0.001). After controlling for height, weight, and age, the CMJ peak power correlated moderately with tibial SSI (r = 0.31, P\0.001) but not with fibular SSI (r = 0.069, P = 0.313). In conclusion, observed differences in the association between neuromuscular performance and tibial and fibular traits suggest
that the tibia and fibula experience different loading

An open source approach for regional cortical bone mineral density analysis

Objective: Cortical porosity, particularly at the endocortical region, is recognised to play a central role in the pathogenesis of bone fragility. Therefore, the purpose of this study was to: 1) demonstrate how cortical volumetric BMD (vBMD) distribution can be analysed from (p)QCT images and 2) highlight the clinical significance of assessing regional density distribution of cortical bone. 

Methods: We used pQCT to compare mid-tibial cortical volumetric BMD distribution of 20 young (age 24(SD2) years, mass 77(11) kg, height 178(6) cm) and 25 elderly (72(4) years, 75(9) kg, 172(5) cm) men. Radial and polar cortical vBMD distributions were analysed using a custom built open source analysis tool which allowed the cortex to be divided into three concentric cortical divisions and in 36 cortical sectors originating from the centroid of the bone.

Results: Mean vBMD did not differ between the groups (1135(16) vs. 1130(28) mg/cm, P=0.696). In contrast, there was a significant age-group by radial division interaction for radial cortical vBMD (P<0.001).

Conclusions: The proposed analysis method for analysing cortical bone density distribution of pQCT images was effective for detecting regional differences in cortical density between young and elderly men, which would have been missed by just looking at mean vBMD values.

Socioeconomic status and bone mineral density in a population-based sample of men

Overall, socioeconomic status (SES) is inversely associated with poorer health outcomes. However, current literature provides conflicting data of the relationship between SES and bone mineral density (BMD) in men. In an age-stratified population-based randomly selected cross-sectional study of men (n = 1467) we assessed the association between SES and lifestyle exposures in relation to BMD. SES was determined by matching the residential address for each subject with Australian Bureau of Statistics 2006 census data for the study region. BMD was measured at the spine and femoral neck by dual energy X-ray absorptiometry. Lifestyle variables were collected by self-report. Regression models were age-stratified into younger and older groups and adjusted for age, weight, dietary calcium, physical activity, and medications known to affect bone. Subjects with spinal abnormalities were excluded from analyses of BMD at the spine. In younger men, BMD was highest at the spine in the mid quintiles of SES, where differences were observed compared to quintile 1 (1–7%, p < 0.05). In older men, the pattern of BMD across SES quintiles was reversed, and subjects from mid quintiles had the lowest BMD, with differences observed compared to quintile 5 (1–7%, p < 0.05). Differences in BMD at the spine across SES quintiles represent a potential 1.5-fold increase in fracture risk for those with the lowest BMD. There were no differences in BMD at the femoral neck. Further research is warranted which examines the mechanisms that may underpin differences in BMD across SES quintiles and to address the current paucity of data in this field of enquiry.

Bone mineral density reference ranges for Australian men : Geelong Osteoporosis Study

Summary : A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations.

Introduction : To provide normative BMD data for Australian men derived from a large population-based random sample.

Methods : An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20–97 years). BMD was quantified at multiple sites using Lunar densitometers.

Results : Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm² per year from age 20. At the hip sites, mean BMD decreased at 0.001–0.006 g/cm² per year from age 20. At the forearm and whole body, BMD peaked at 41–47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain.

Conclusions : These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.

β-Adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density : Geelong Osteoporosis Study

This population-based study documented β-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with β-blocker use was 0.68 (95%CI, 0.49–0.96). β-Blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. β-Blocker use is associated with reduced fracture risk and higher BMD.

Introduction: Animal data suggests that bone formation is under β-adrenergic control and that β-blockers stimulate bone formation and/or inhibit bone resorption.

Materials and Methods: We evaluated the association between β-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. β-Blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire.

Results: Odds ratio for fracture associated with β-blocker use was 0.68 (95% CI, 0.49–0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. β-Blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use.

Conclusion: β-Blockers are associated with a reduction in fracture risk and higher BMD.

Statin use, bone mineral density, and fracture risk: Geelong Osteoporosis Study

Background Recent data suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease fracture risk and increase bone mineral density (BMD).

Methods This cross-sectional study is set in southeastern Australia. We evaluated the association between statin use, fracture risk, and BMD in 1375 women (573 with incident fractures and 802 without incident fracture, all drawn from the same community). Fractures were identified radiologically. Medication use and lifestyle factors were documented by questionnaire.

Results Unadjusted odds ratio for fracture associated with statin use was 0.40 (95% confidence interval [CI], 0.23-0.71). Adjusting for BMD at the femoral neck, spine, and whole body increased the odds ratio to 0.45 (95% CI, 0.25-0.80), 0.42 (95% CI, 0.24-0.75), and 0.43 (95% CI, 0.24-0.78), respectively. Adjusting for age, weight, concurrent medications, and lifestyle factors had no substantial effect on the odds ratio for fracture. Statin use was associated with a 3% greater adjusted BMD at the femoral neck (P = .08), and BMD tended to be greater at the spine and whole body but did not achieve statistical significance.

Conclusion The substantial 60% reduction in fracture risk associated with statin use is greater than would be expected from increases in BMD alone.

Forearm bone mineral density and incidence of hip fractures in Swedish urban and rural men 1987-2002

Background: It is not known whether the recently described break in the trend in hip fracture incidence in many settings applies in both women and men, depends on changes in bone mineral density (BMD) or changes in other risk factors, or whether it is apparent in both urban and rural settings. Methods: We evaluated changes in annual hip fracture incidence from 1987 to 2002 in Swedish men aged ≥60 years in one urban (n=25,491) and one rural population (n=16,432) and also secular differences in BMD, measured by single-photon absorptiometry at the distal radius and multiple other risk factors for hip fracture in a population-based sub-sample of the urban and the rural men aged 60–80 years in 1988/89 (n=202 vs. 121) and in 1998/99 (n=79 vs. 69). Results: No statistically significant changes in the annual age-adjusted hip fracture incidence per 10,000 were apparent from 1987 to 2002 in urban (0.38 per year, 95% CI-0.12 to 0.88) or rural men (-0.05 per year, 95% CI -0.63 to 0.53). BMD was similar in 1988/89 and 1998/99 when examining both urban (-19.6 mg/cm², 95% CI -42.6 to 3.5) and rural (-23.0 mg/cm², 95% CI -52.1 to 6.1) men. Conclusions: Since no secular change in age-adjusted hip fracture incidence was found during the study period, a levelling off in hip fracture incidence is present also in Swedish men. Because BMD on a group level was similar in 1988/89 and 1998/99, changes in other risk factors ought to be either of minor importance or counteracted by changes in different risk factors.

Social disadvantage, bone mineral density and vertebral wedge deformities in the Tasmanian Older Adult Cohort

Summary The relationship between social disadvantage and bone mineral density (BMD) is complex and remains unclear; furthermore, little is known of the relationship with vertebral deformities. We observed social disadvantage to be associated with BMD for females, independent of body mass index (BMI). A lower prevalence of vertebral deformities was observed for disadvantaged males.

Introduction The relationship between social disadvantage and BMD appears complex and remains unclear, and little is known about the association between social disadvantage and vertebral wedge deformities. We examined the relationship between social disadvantage, BMD and wedge deformities in older adults from the Tasmanian Older Adult Cohort.

Methods BMD and wedge deformities were measured by dual-energy X-ray absorptiometry and associations with extreme social disadvantage was examined in 1,074 randomly recruited population-based adults (51 % female). Socioeconomic status was assessed by Socio-economic Indexes for Areas values derived from residential addresses using Australian Bureau of Statistics 2001 census data. Lifestyle variables were collected by self-report. Regression models were adjusted for age, BMI, dietary calcium, serum vitamin D (25(OH)D), smoking, alcohol, physical inactivity, calcium/vitamin D supplements, glucocorticoids and hormone therapy (females only).

Results Compared with other males, socially disadvantaged males were older (65.9 years versus 61.9 years, p = 0.008) and consumed lower dietary calcium and alcohol (both p ≤ 0.03). Socially disadvantaged females had greater BMI (29.9 ± 5.9 versus 27.6 ± 5.3, p = 0.002) and consumed less alcohol (p = 0.003) compared with other females. Socially disadvantaged males had fewer wedge deformities compared with other males (33.3 % versus 45.4 %, p = 0.05). After adjustment, social disadvantage was negatively associated with hip BMD for females (p = 0.02), but not for males (p = 0.70), and showed a trend for fewer wedge deformities for males (p = 0.06) but no association for females (p = 0.85).

Conclusions Social disadvantage appears to be associated with BMD for females, independent of BMI and other osteoporosis risk factors. A lower prevalence of vertebral deformities was observed for males of extreme social disadvantage. Further research is required to elucidate potential mechanisms for these associations.

Gender specific age-related changes in bone density, muscle strength and functional performance in the elderly: a-10 year prospective population-based study

Background: