Obesity, bone density relative to body weight and prevalent vertebral fracture at age 62 years: the Newcastle thousand families study.

Obesity increases the likelihood of prevalent vertebral fracture (VF) in men and women at age 62 years. The higher absolute bone mineral density (BMD) observed in obese individuals is disproportionate to body weight, and this may partly explain the greater prevalence of VF in this group. INTRODUCTION: Obesity is a global epidemic, and there remains uncertainty over the effect of obesity on skeletal health, particularly in the context of osteoporosis. The aim of this study was to investigate associations of body mass index (BMI) and obesity with BMD and prevalent VF in men and women aged 62 years. METHODS: Three hundred and forty-two men and women aged 62.5 ± 0.5 years from the Newcastle Thousand Families Study birth cohort underwent DXA evaluations of femoral neck and lumbar spine BMD and of the lateral spine for vertebral fracture assessment. RESULTS: The likelihood of prevalent VF was significantly increased in men when compared to women (OR = 2.7, p < 0.001, 95% Cl 1.7-4.4). As BMI increased in women, so did the likelihood of prevalent any-grade VF (OR = 1.09, p = 0.006, 95% CI 1.02-1.17). Compared to normal weight women, obese women were more likely to have at least one VF (OR = 2.65, p = 0.025, CI 1.13-6.20) and at least one grade 1 vertebral deformity (OR = 4.39, p = 0.005, CI 1.57-12.28). Obese men were more likely to have a grade 2 and/or grade 3 VF compared to men of normal weight (OR = 3.36, p = 0.032, CI 1.11-10.16). In men and women, BMI was negatively associated with femoral neck BMD/weight (R = - 0.65, R = - 0.66, p < 0.001) and lumbar spine BMD/weight (R = - 0.66, R - 0.60, p < 0.001). CONCLUSIONS: Obesity appears to be a risk factor for prevalent VF, and although absolute BMD is higher in obese individuals, this does not appear commensurate to their increased body weight.

Does regional loss of bone density explain low trauma distal forearm fractures in men (the Mr F study)?

The pathogenesis of low trauma wrist fractures in men is not fully understood. This study found that these men have lower bone mineral density at the forearm itself, as well as the hip and spine, and has shown that forearm bone mineral density is the best predictor of wrist fracture. INTRODUCTION: Men with distal forearm fractures have reduced bone density at the lumbar spine and hip sites, an increased risk of osteoporosis and a higher incidence of further fractures. The aim of this case-control study was to investigate whether or not there is a regional loss of bone mineral density (BMD) at the forearm between men with and without distal forearm fractures. METHODS: Sixty-one men with low trauma distal forearm fracture and 59 age-matched bone healthy control subjects were recruited. All subjects underwent a DXA scan of forearm, hip and spine, biochemical investigations, health questionnaires, SF-36v2 and Fracture Risk Assessment Tool (FRAX). The non-fractured arm was investigated in subjects with fracture and both forearms in control subjects. RESULTS: BMD was significantly lower at the ultradistal forearm in men with fracture compared to control subjects, in both the dominant (mean (SD) 0.386 g/cm2 (0.049) versus 0.436 g/cm2 (0.054), p < 0.001) and non-dominant arm (mean (SD) 0.387 g/cm2 (0.060) versus 0.432 g/cm2 (0.061), p = 0.001). Fracture subjects also had a significantly lower BMD at hip and spine sites compared with control subjects. Logistic regression analysis showed that the best predictor of forearm fracture was ultradistal forearm BMD (OR = 0.871 (0.805-0.943), p = 0.001), with the likelihood of fracture decreasing by 12.9% for every 0.01 g/cm2 increase in ultradistal forearm BMD. CONCLUSIONS: Men with low trauma distal forearm fracture have significantly lower regional BMD at the ultradistal forearm, which contributes to an increased forearm fracture risk. They also have generalised reduction in BMD, so that low trauma forearm fractures in men should be considered as indicator fractures for osteoporosis.

Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study.

SUMMARY: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown. INTRODUCTION: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N). METHODS: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models. RESULTS: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) µg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort. CONCLUSION: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

Magnitude of fragility fracture risk in the very old--are we meeting their needs? The Newcastle 85+ Study.

UNLABELLED: Fractures due to osteoporosis are common in older people. This study assessed the management of osteoporosis in a group of 85-year-olds and found both assessment and current treatment to be suboptimal. INTRODUCTION: Fragility fractures are a major cause of excess mortality, substantial morbidity, and health and social service expenditure in older people. However, much less is known about fracture risk and its management in the very old, despite this being the fastest growing age group of our population. METHODS: Cross-sectional analysis of people who reached the age of 85 during the year of 2006 was carried out. Data were gathered by general practice record review (GPRR) and a multidimensional health assessment (MDHA). RESULTS: Seven hundred thirty-nine individuals were recruited. Mean age was 85.55 years (SD 0.44), and 60.2% were female; 33.7% (n = 249) had experienced one or more fragility fractures (F 45.2% vs M 16.3% p < 0.001); in total, 332 fractures occurred in these 249 individuals. A formal documented diagnosis of osteoporosis occurred in 12.4%, and 38% of individuals had experienced a fall in the last 12 months. When the fracture risk assessment tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidelines were applied, osteoporosis treatment would be recommended in 35.0%, with a further 26.1% identified as needing bone mineral density (BMD) measurement and 38.9% not requiring treatment or BMD assessment. Women were more likely than men to need treatment (47.4 vs 16.3%, p < 0.001, odds ratio (OR) 4.62 (3.22-5.63)) and measurement of BMD (40.0 vs 5.1%, p < 0.001, OR 12.4 (7.13-21.6)). Of the 259 individuals identified as requiring treatment, only 74 (28.6%) were on adequate osteoporosis treatment. CONCLUSION: The prevalence of high fracture risk in the very old is much higher than the documented diagnosis of osteoporosis or the use of adequate treatments.

FRAX-based assessment and intervention thresholds--an exploration of thresholds in women aged 50 years and older in the UK.

UNLABELLED: Under current guidelines, based on prior fracture probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold (a fixed threshold from the age of 70 years) reduces this disparity, increases treatment access and decreases the need for bone densitometry. INTRODUCTION: Several international guidelines set age-specific intervention thresholds at the 10-year probability of fracture equivalent to a woman of average BMI with a prior fracture. At older ages (≥70 years), women with prior fracture selected for treatment are at lower average absolute risk than those selected for treatment in the absence of prior fracture, prompting consideration of alternative thresholds in this age group. METHODS: Using a simulated population of 50,633 women aged 50-90 years in the UK, with a distribution of risk factors similar to that in the European FRAX derivation cohorts and a UK-matched age distribution, the current NOGG intervention and assessment thresholds were compared to one where the thresholds remained constant from 70 years upwards. RESULTS: Under current thresholds, 45.1% of women aged ≥70 years would be eligible for therapy, comprising 37.5% with prior fracture, 2.2% with high risk but no prior fracture and 5.4% selected for treatment after bone mineral density (BMD) measurement. Mean hip fracture probability was 11.3, 23.3 and 17.6%, respectively, in these groups. Under the alternative thresholds, the overall proportion of women treated increased from 45.1 to 52.9%, with 8.4% at high risk but no prior fracture and 7.0% selected for treatment after BMD measurement. In the latter group, the mean probability of hip fracture was identical to that observed in women with prior fracture (11.3%). The alternative threshold also reduced the need for BMD measurement, particularly at older ages (>80 years). CONCLUSIONS: The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages.

Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis.

UNLABELLED: The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity. INTRODUCTION: RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption. METHODS: Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, ß-isomerised carboxy-terminal telopeptide of type 1 collagen [ßCTX] and osteoprotegerin [OPG]). RESULTS: A significant decrease in bone resorption was observed 6 months after rituximab (median change ßCTX -50 ng/L, 95%CI -136, -8 p < 0.001, this equates to -37%; 95%CI -6, -49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0 µg/L, 95%CI -1.0, 11.2, p = 0.02; 13%; 95%CI -3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of ßCTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r (s) = 0.570, p = 0.014). CONCLUSIONS: In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity.

Proceedings of the Rank Forum on Vitamin D.

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of 'optimal' concentration of serum 25(OH)D needs to define 'optimal' with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Plasma vitamin D and cytokines in periodontal disease and postmenopausal osteoporosis.

BACKGROUND AND OBJECTIVE: Osteoporosis and periodontal disease are chronic diseases, in the pathogenesis of which plasma osteoprotogerin (OPG) and RANKL are important. The study aimed to investigate the relationship between periodontal disease and plasma cytokines, vitamin D and bone mineral density in postmenopausal women with and without osteoporosis. MATERIAL AND METHODS: One hundred and eighty-five postmenopausal women with osteoporosis and 185 age- and sex-matched control subjects were recruited. Periodontal disease was subdivided into active or past periodontal disease. Osteoprotegerin, RANKL, 25-hydroxyvitamin D3 (25OHD), biochemical markers of bone turnover (serum C-terminal telopeptide, CTX), anthropometry and bone mineral density were measured. RESULTS: A significantly higher proportion of the women with osteoporosis had active or past periodontal disease or both compared with control subjects (87.6 vs. 37.8%, p < 0.001). Plasma 25OHD was significantly lower (p < 0.001) and RANKL and OPG significantly higher in the women with osteoporosis than in control subjects (p < 0.0001). RANKL, OPG and CTX were significantly higher in women with active periodontal disease than in those without (p < 0.001), as were OPG and CTX in past periodontal disease (p < 0.001). In active and past periodontal disease, 25OHD was significantly lower (p < 0.001). Multiple logistic regression analysis showed that periodontal disease was best predicted by RANKL, 25OHD, C-terminal telopeptide and weight, r² = 10.4%. CONCLUSION: Periodontal disease is more common in women with osteoporosis and is associated with lower vitamin D and higher concentrations of RANKL and OPG. Raised cytokines may provide the underlying mechanism that links these two conditions.

Hormone replacement therapy (HRT) or etidronate for osteoporosis in postmenopausal asthmatics on glucocorticoids: a randomised factorial trial.

INTRODUCTION: The study was designed to establish the effects of HRT on osteoporosis and fractures over five years in postmenopausal women with asthma receiving regular glucocorticoids and to compare with etidronate. METHODS: Postmenopausal patients receiving inhaled and/or oral glucocorticoids were randomly assigned to HRT, cyclical etidronate, HRT plus cyclical etidronate or no treatment for five years. The trial was multi-centre and aimed to recruit 750 patients. Outcomes were fractures and changes in bone mineral density (BMD). RESULTS: For reasons detailed in the discussion section of the text, only 50 patients were entered. Three did not fulfil the eligibility criteria and were excluded from the analysis. Among the remaining 47 patients, three (6%) experienced new, symptomatic fractures, one on etidronate and two in the no treatment group. New or worsening morphometric fractures of the thoracolumbar spine occurred in 50% of the 22 patients with spinal radiographs on entry and at five years (one HRT, three etidronate, two HRT plus etidronate and five on no treatment). BMD improved by approximately 1% per annum in those receiving HRT and/or etidronate; comparisons of HRT vs no HRT tended to favour HRT but were only statistically significant at proximal femur. The same trends emerged in the etidronate vs no etidronate comparison, but none reached the 5% level of statistical significance. DISCUSSION: For postmenopausal patients receiving glucocorticoids for asthma, HRT appears as effective as etidronate in preventing loss of BMD over five years and may have a similar effect on fracture prevention.

No effect of monthly supplementation with 12000 IU, 24000 IU or 48000 IU vitamin D3 for one year on muscle function: The vitamin D in older people study.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

pophelper: an R package and web app to analyse and visualize population structure.

The pophelper r package and web app are software tools to aid in population structure analyses. They can be used for the analyses and visualization of output generated from population assignment programs such as admixture, structure and tess. Some of the functions include parsing output run files to tabulate data, estimating K using the Evanno method, generating files for clumpp and functionality to create barplots. These functions can be streamlined into standard r analysis workflows. The latest version of the package is available on github (https://github.com/royfrancis/pophelper). An interactive web version of the pophelper package is available which covers the same functionalities as the r package version with features such as interactive plots, cluster alignment during plotting, sorting individuals and ordering of population groups. The interactive version is available at http://pophelper.com/.

Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.

BACKGROUND: Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures. METHODS: In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures. FINDINGS: 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups. INTERPRETATION: The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

Calcaneal bone mineral density in older patients who have fallen.

BACKGROUND: Annually, 35-40% of those aged >65 years fall; up to 5% of such falls result in fracture. Fracture is determined both by propensity to fall and by bone fragility. AIM: To determine osteoporosis prevalence and predictors in patients who have fallen. DESIGN: Observational cross-sectional study. METHODS: We measured calcaneal BMD in 408 consecutive patients aged >50 years attending after falling. Fall number, fracture history, weight, height, and risk factors for falls and osteoporosis were recorded. T scores (SD above or below the mean for young adults) were derived in both sexes, and Z scores (SD above or below age-related normal score) in females. RESULTS: In females (n = 300, 74%), mean (SD) T score was -1.1(1.6), and mean Z score was 0(1.4); 127 (42%) had osteoporosis (T score < - 1.6). ROC curves confirmed significant relationships between osteoporosis and age, weight and height (all p < 0.0001). Incorporating fracture history, our model (fracture aged >50 years, age >83 years, weight <57 kg, height <153 cm as dichotomous variables) predicted osteoporosis with 91% sensitivity, 34% specificity. Of 108 male fallers, 36 (33%) had osteoporosis. Age, height and weight all predicted osteoporosis (p < 0.02). The resulting model (fracture aged >50 years, age > or =80 years, weight < or =68 kg, height < or =167 cm as dichotomous variables) predicted osteoporosis with 92% sensitivity, 30% specificity. DISCUSSION: Osteoporosis prevalence is not increased in female fallers compared to age-related norms; empirical use of osteoporosis treatment solely on the basis of falls thus appears inappropriate. In both sexes, the factors predicting osteoporosis were age, height and weight. Where BMD is not practical, possible or economical, our model may be a sensitive means of predicting fallers with osteoporosis.

Differences in bone mineral density and geometry in men and women: the Newcastle Thousand Families Study at 50 years old.

In 1947 Sir James Spence initiated the Newcastle Thousand Families study, which recruited all 1142 children born in the city between May and June that year. At the age of 50 years, 832 survivors were traced and invited to attend for measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). The aim was to compare BMD measurements of men and women in this cohort, before and after adjustment for skeletal size. The femoral neck shaft angles (NSA) were also measured manually from the DXA scan printouts. A total of 171 men and 218 women agreed to participate. As expected men had greater bone mineral content and bone area at all sites (p<0.0001) and were taller and heavier (p<0.0001) than women. Men also had significantly higher BMD than women at all regions (p<0.0002), except at the femoral neck or lumbar spine. After correction for skeletal size and body weight, men had statistically significantly lower volumetric BMD at all sites. The measurement of NSA had good intra/interobserver errors and precision (coefficient of variations 0.79%, 1.2% and 1.2%). Men had significantly larger NSAs (mean 130 degrees , range 121-138 degrees ) than women (mean 128 degrees , range 119-137 degrees ). We conclude that there are gender differences in BMD, skeletal size and geometry in middle aged men and women, which together with the subsequent rate of bone loss, may influence fracture risk in later life.

Low bone mineral content is common but osteoporotic fractures are rare in elderly rural Gambian women.

Osteoporosis is reported to be rare in Black Africa. The low fracture incidence among North American black women is explained by a high peak bone mass and preservation of bone mineral into old age. To assess whether this is the case among Black African women, we measured bone mineral content (BMC) and bone mineral density (BMD), using single- and dual-photon absorptiometry, in 195 rural Gambian women aged over 44 years and 391 white women of comparable age from three centers in the U.K. Measurements were made at the midshaft of the radius, distal radius, lumbar spine, and femoral neck. The influence of height, weight, and nationality on BMC and BMD was analyzed. BMC and BMD decreased with age at all sites. Age, decreasing weight, but not height were independently associated with lower BMC at all sites. BMC in Gambian women was lower than in British women by 31% at the lumbar spine and 16% at the midshaft of the radius. After adjustment for age, height, and weight, BMC among Gambian women remained 24% lower at the lumbar spine and 10% lower at the radius. In women aged over 64 years, BMC at the lumbar spine was 42% lower and BMD was 31% lower in The Gambia (for all comparisons, p < 0.005). We conclude that bone mineral mass is not preserved in elderly Gambian women. However, minimal trauma fractures are rare in this population. These results challenge the concept of BMC as a primary determinant of fracture risk.

Androgen supplementation in eugonadal men with osteoporosis: effects of six months' treatment on markers of bone formation and resorption.

There is no established treatment for osteoporosis in men, a common and disabling condition the incidence of which is increasing rapidly. We conducted an open study to investigate the efficacy and mode of action of testosterone therapy in eugonadal men with osteoporotic vertebral crush fracture. Twenty-one men, aged 34-73 (mean 58), were treated with intramuscular testosterone esters (Sustanon 250) every 2 weeks for 6 months. Bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry was performed at baseline and 6 months. We also measured biochemical markers of bone turnover, testosterone, estradiol, sex hormone binding globulin (SHBG), and gonadotrophins at baseline and after 3 and 6 months of treatment. Treatment was well tolerated, and side effects were uncommon. Lumbar spine BMD increased by 5% from 0.799 to 0.839 g/cm2 (p < 0.001). All bone markers decreased, indicating that treatment suppressed bone turnover. Although serum osteocalcin levels fell only slightly, there were large reductions in urinary deoxypyridinoline and N-telopeptide (p < 0.05), which were correlated with the increase in spinal BMD. Interpretation of the findings with other markers, such as bone-specific alkaline phosphatase and pyridinoline, was confounded by the wide scatter of values. Serum testosterone increased by 55%, while SHBG decreased by 20%, leading to a rise in free androgen of 90%. Serum estradiol also increased by 45%. The change in spine BMD was significantly correlated with a change in serum estradiol but not with a change in serum testosterone. We therefore conclude that testosterone is a promising treatment for men with idiopathic osteoporosis, acting to suppress bone resorption by a mechanism that may involve estrogen.

Local action of oral 1,25-dihydroxycholecalciferol on calcium absorption in osteoporosis.

To investigate whether low calcium absorption in osteoporosis improves by increasing 1,25-dihydroxyvitamin D both systemically in plasma and locally in gut, the effects of oral 25-hydroxycholecalciferol and oral 1,25-dihydroxycholecalciferol on plasma 1,25-dihydroxy-vitamin D (1,25-(OH)2D) and calcium absorption were studied in 20 postmenopausal patients with vertebral osteoporosis. In 10 patients taking oral 0.25 micrograms 1,25-dihydroxycholecalciferol twice daily for 7 d, calcium absorption increased more than in 10 patients taking oral 40 micrograms 25-hydroxycholecalciferol once daily for 7 d (p less than 0.02) despite both groups having a similar increase in plasma 1,25-(OH)2D. These results support the view that the major effects of oral 1,25-dihydroxycholecalciferol on absorption is due to a local action on the gut and that it is possible to increase calcium absorption in osteoporosis with oral 1,25-dihydroxycholecalciferol without increasing its undesirable action on bone resorption.

A comparison of the effect of sorbitol and glucose on calcium absorption in postmenopausal women.

It has been suggested that the oral administration of sorbitol promotes calcium absorption, while glucose has no effect. We have therefore compared the effect of oral sorbitol and glucose on the absorption of radiocalcium from low and high carrier loads in healthy postmenopausal women. In a control group of 20 women given neither sorbitol nor glucose, the mean +/- SEM fractional radiocalcium absorption rate from a low carrier load was 0.65 +/- 0.05 (fraction of dose/h). In a second group of 10 women the fractional absorption rate from the low carrier load was lower (p less than 0.05) with 10 g sorbitol (0.48 +/- 0.05) than with 10 g glucose (0.65 +/- 0.08). Fractional absorption of radiocalcium from a high carrier load measured in a third group of seven women using two isotopes (oral 45Ca, IV 47Ca) was also lower (p less than 0.001) with 10 g sorbitol (0.22 +/- 0.01, fraction/3 h) than with 10 g glucose (0.29 +/- 0.02). The results suggest that calcium absorption from a low carrier load is unaltered by glucose but that absorption of calcium from both low and high carrier loads is lower with sorbitol than with glucose.