Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis

OBJECTIVE The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect Inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD. DESIGN Case-control studies of patients on long-term T4 therapy who have or have not previously received radio-iodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement. PATIENTS Twenty-seven premenopausal and 60 post-menopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group l), 39 post-menopausal females with a past history of radio-iodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post-menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status. MEASUREMENTS BMD measured by dual-energy X-ray absorptiometry. Serum biochemistry and tests of thyroid function. RESULTS No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post-menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences In BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3·9%, P <0·05) and lumbar spine (5·6–8·5%, P <0·01) BMD results were found in post-menopausal females In group 1 and reductions in femoral trochanter (3·9%, P <0·01), Ward's triangle (5·6%, P <0·05) and lumbar spine (8·5%, P <0·01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group. CONCLUSIONS Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post-menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.     

ORIGINAL ARTICLE: The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men

Objective Although osteoporosis is increasingly shown to occur in a considerable proportion of men, data on risk factors for male osteoporosis are limited. In this study, we investigated the association between serum thyrotropin (TSH) concentration and bone mineral density (BMD) in healthy euthyroid men. Design A cross‐sectional community (health promotion centre)‐based survey. Subjects and measurements For 1478 apparently healthy euthyroid men who participated in a routine health screening examination, we measured BMD at the lumbar spine and femoral neck using dual energy X‐ray absorptiometry and serum TSH concentrations using immunoluminometry. Results Lumbar spine BMD linearly increased with TSH level after adjustment for age, weight and height (P for trend = 0·002), and statistical significance persisted after additional adjustment for smoking and drinking habits (P for trend = 0·010). When serum alkaline phosphatase was added as a confounding variable, the relationship was still significant (P for trend = 0·016). Femoral neck BMD also tended to increase in higher TSH concentration after adjustment for age, weight and height (P for trend = 0·042), but this association disappeared after additional adjustment for smoking and drinking habits. The odds of lower BMD (i.e. osteopaenia and osteoporosis combined) were significantly increased in subjects with low‐normal TSH (i.e. 0·4–1·2 mU/l), when compared to high‐normal TSH (i.e. 3·1–5·0 mU/l), after adjustment for confounding factors (odds ratio = 1·45, 95% CI = 1·02–2·10). Conclusion These results suggest that a serum TSH concentration at the lower end of the reference range may be associated with low BMD in men.     

Effects of serum TSH and FT4 levels and the TSHR-Asp727Glu polymorphism on bone: the Rotterdam Study

Background TSH and thyroid hormone may have independent effects on bone. In this study we investigated the association of TSH and free T4 (FT4) with different bone parameters in human subjects. TSH and FT4 are known to be associated with body mass index (BMI) and a higher BMI gives a higher bone mineral density (BMD). Thus, we aimed to determine whether the effects of TSH and FT4 on bone are mediated by BMI. As TSH exerts its biological effect through the TSH receptor (TSHR), the TSHR gene might be a candidate gene affecting bone mass. The TSHR‐Asp727Glu polymorphism is associated with lower TSH levels. We therefore examined the association of this polymorphism with bone parameters. Method Genotypes were determined by Taqman assay in 4934 elderly Caucasian men and women of the Rotterdam Study, of whom BMD and bone geometry data were available. Serum thyroid parameters were available in a random set of 1327 subjects,. Results Femoral neck BMD as well as narrow neck BMD and cortical thickness increased with serum TSH. However, FT4 was more strongly and negatively associated with bone parameters. Regression models showed BMI‐dependent and ‐independent effects of both TSH and FT4 on bone. Carriers of the TSHR‐Glu⁷²⁷ allele had a 2·3% higher femoral neck BMD. Conclusion In line with the effect of TSH on bone in mice, serum TSH shows a positive trend with BMD in human subjects, a finding that is strengthened by the association between the TSHR‐Asp727Glu polymorphism and femoral neck BMD. However, serum FT4 has a much greater influence on bone than TSH.     

Serum testosterone and its relation to bone mineral density and body composition in normal males

OBJECTIVE Bone mineral density (BMD) declines with age in both men and women, predisposing the elderly to osteoporosis and fractures. Although there are extensive data about post-menopausal osteoporosis, there is relatively little information concerning the decrease in BMD with age in normal men, particularly the contribution of declining gonadal function with age to BMD. In the present study, we investigated the effect of age on the pituitary-gonadal axis in normal males and its relation to BMD and body composition. SUBJECTS Ninety healthy Thai males in the Bangkok Metropolitan area without a history of smoking or significant alcohol consumption were studied. MEASUREMENTS Serum testosterone (T), free testosterone (FT), LH and FSH were measured by radioimmunoassay in fasting blood samples obtained In the morning between 0600 and 1000h. BMD at anteroposterior L2-L4, lateral L2-L4, femoral neck, femoral trochanter and Ward's triangle were determined by dual-energy X-ray absorptiometry. RESULTS There were significant declines with age in BMD at lateral L2-L4 (r= 0.37, P < 0.001), femoral neck (r=?0.49, P<0.0001), Ward's triangle (r=?0.54, P < 0.0001) but not at anteroposterior L2-L4 or femoral trochanter. Serum FT (r=?0.56, P < 0.0001) but not T (r=?0.19, P= 0.07) decreased with age. Serum LH (r= 0.27, P <0.001) and FSH (r= 0.4, P <0.0001) increased with age suggesting a defect in gonadal androgen synthesis or possibly a secretion of bioinactive LH. Serum FT concentrations were significantly correlated to lateral L2-L4 (r= 0.27, P<0.05), femoral neck (r= 0.48, P < 0.0001) and Ward's triangle (r= 0.50, P < 0.0001) BMD. After controlling for age, declining FT with age was still associated with a decrease In BMD in femoral neck (P < 0.05) and Ward's triangle (P < 0.05) but not in lateral L2-L4. The proportion of body fat increased with age (r= 0.3, P < 0.01). Decreased serum T, but not FT, was associated with increased body fat after age was taken into account (P < 0.0001). CONCLUSIONS There is a decline in serum free testosterone together with increases In LH and FSH with age In healthy males. The decrease in serum free testosterone Is partially associated with the age-related decline in bone mineral density added to the effect of age at the femoral neck and Ward's triangle. Testosterone but not free testosterone Is associated with age-related increase in body fat.     

Loss of trabecular bone mineral density in systemic lupus erythematosus

Objective. To evaluate trabecular bone mineral density (BMD) in young ambulatory female patients with systemic lupus erythematosus (SLE). Methods. Bone mineral density (gm/cm²) at the lumbar vertebrae (L1–L4) and at the left femur (neck, trochanter, intertrochanter, and Ward's triangle) was measured by dual x-ray absorptiometry in 46 SLE patients (mean age 31 years, mean disease duration 76 months) and in 108 healthy female controls (mean age 32 years). Twenty-two of the SLE patients were receiving corticosteroids (CS) at the time of the study. Results. Lumbar BMD in the SLE patients was less severely reduced than was BMD at the femoral sites, but the SLE group was closer to the lumbar fracture threshold of 0.812 gm/cm² than was the control group (P = 0.0009). There were no significant differences between the SLE patients currently being treated with corticosteroids and those who were not (P > 0.3). BMD at Ward's triangle and at the femoral neck was not significantly reduced in the SLE patients. Total femoral BMD had a sensitivity of 76% and specificity of 62% in differentiating the SLE group from the controls. The positive predictive value was 61% and the negative predictive value was 89%. The prevalence of osteopenia in the SLE patients was 25%. Conclusion. SLE causes significant trabecular bone loss, which is not due to corticosteroid therapy.     

Thyroxine suppressive therapy decreases bone mineral density in post-menopausal women

OBJECTIVE Hyperthyroidism is associated with increased bone turnover and decreased bone mass. This study aimed to evaluate the bone mineral density (BMD) of post-menopausal women on long-term thyroxine suppressive therapy. DESIGN An age and sex-matched cross-sectional study. PATIENTS Thirty-four post-menopausal women with carcinoma of thyroid, post total thyroidectomy nd M ablation, on L-T4 for 12 2 ± 6–6 years (mean±SD). Controls were 34 age-matched healthy Southern Chinese women. MEASUREMENTS Total body and regional BMDs were determined by dual-energy X-ray absorptiometry. Bone turnover was assessed by biochemical markers. RESULTS In the thyroxine treated group, total body mineral content was significantly lower than the controls (1652±356 vs 1994±270 g meaniSD, P<0 005). They also had lower BMDs in the lumbar spine, femoral neck, trochanter and Ward's triangle (0 75 ± 0 15 vs 0 92 ± 0 16 g/ cm2, P<0005; 0–62±0–12 vs 0–70±0–12 g/cm2, P<0–01; 0–55±0–14 vs 063±015 g/cm2, P<0.001; 055±014 vs 0–63 ±0–14 g/cm², P < 0.005 respectively.) The thyroxine treated group also had higher serum alkaline phosphatase and osteocalcin levels as well as urinary hydroxypro-line excretion, suggesting that they had high turnover bone loss. However, the Z-scores of the various regional BMDs were correlated only with the serum osteocalcin level and showed no correlation with the serum thyroxine level or with the dosage or duration of thyroxine treatment. CONCLUSION Long-term thyroxine suppressive therapy was associated with bone loss and preventive therapy may be indicated in these post-menopausal women at risk of osteoporosis.     

Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine

OBJECTIVE The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover. DESIGN A prospective study over 2 years of postmenopausal women treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND MEASUREMENTS Sixty-four postmenopausal women, ages 47 to 74 (61 ±9, mean ± SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n =23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n =23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2. RESULTS The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = ?0.41 P < 0.001, r = ?0.29 P =0.01 and r = ?0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow-up (ANOVA, P >0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t-test, P =0.0021, 0.034, 0.0017, 0.011 and >0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P <0.05). CONCLUSIONS In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.     

Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake

OBJECTIVE The bisphosphonates have proven efficacy in the management of post-menopausal osteoporosis. However, the benefits of prolonged (<2 years) administration and the effects of discontinuation of bisphosphonate treatment are not clear. DESIGN We have previously reported a 2-year, randomized, double-blind, placebo-controlled trial of pamidronate therapy (150mg/day) in women with established post-menopausal osteoporosis. We now report the bone mineral density (BMD) changes in those women who continued for a third year of active treatment and were then observed off therapy for a further 12 months. PATIENTS Twenty-two women (mean age 66 years) continued on pamidronate in year 3, and in 16 of these the effects of subsequent discontinuation of therapy for 12 months were studied. MEASUREMENTS BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer. RESULTS The third year of therapy with pamidronate was associated with a significant further gain in BMD only at the lumbar spine (2.1±0.8%, P=0.003), resulting in a total gain of 9.5±1.0% at that site over 3 years of treatment. In the total body, BMD tended to decline (?0.6±0.3%) in year 3. One year after discontinuation of pamidronate, there were significant losses of BMD in the total body (?1.9±0.3%, P<0.0001) and femoral trochanter (?2.7±0.9%, P=0.01), and non-significant changes at the lumbar spine (?0.9±0.8%), femoral neck (?0.5±1.6%), and Ward's triangle (?2.9±3.7%). By the end of one year off therapy, BMD was greater than baseline only in the lumbar spine (71±1.1%, P<0.0001) and femoral trochanter (4.5±1.88%, P<0.03). In the total body, BMD was 0.3±0.7% below the values at the trial’s inception (P=0.7). CONCLUSIONS These data demonstrate that the rate of bone gain associated with bisphosphonate use slows over time, and that significant bone loss follows withdrawal of these agents. These findings have important implications for the duration of use of these novel drugs in the therapy of osteoporosis and suggest a need for close observation following their discontinuation.     

Discrepant influence of vitamin D status on parathyroid hormone and bone mass after two years of calcium supplementation

Objective To investigate the influence of vitamin D status on parathyroid hormone and bone mass after a 2‐year supplementation of calcium alone. Patients and Methods Randomized, double‐blind, placebo‐controlled clinical trial, in healthy postmenopausal women without osteoporosis: three hundred and thirty‐six subjects aged 60–97 years were studied and randomized to receive elemental calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. Measurements Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline and vitamin D status. Values are presented as means ± SD. Results After 2 years, subjects with calcium supplementation had significant decrease in plasma PTH level (4·4 ± 1·7 vs 4·7 ± 1·9 pmol/l, P < 0·01), improved lumbar BMD (1·031 ± 0·12 vs 1·004 ± 0·12 g/cm², P < 0·001) and total hip BMD (0·890 ± 0·10 vs 0·883 ± 0·10 g/cm², P < 0·001) without change in femoral neck BMD. In the placebo group, PTH level significantly increased (4·8 ± 1·6 vs 4·5 ± 1·5 pmol/l, P < 0·001), lumbar BMD slightly increased (1·027 ± 0·14 vs 1·018 ± 0·14 g/cm², P < 0·001), total hip and femoral neck BMD decreased (0·876 ± 0·11 vs 0·887 ± 0·11 g/cm², P < 0·001 and 0·783 ± 0·10 vs 0·798 ± 0·10 g/cm², P < 0·001, respectively). When subjects were classified according to baseline 25‐hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the lower tertile (lowVitD) and those in the middle and upper tertiles combined (normVitD). The degree of PTH suppression after calcium supplementation was significantly higher in the normVitD compared to the lowVitD groups (?5·6 ± 26·7%vs 1·3 ± 27·2%, P < 0·05). No effect of vitamin D status on the change in lumbar BMD after calcium supplementation was demonstrated. Despite the higher suppression of PTH, there was a slight decrease in femoral neck BMD after calcium supplementation in the normVitD group while femoral neck BMD was more or less maintained in the lowVitD group (?0·6 ± 3·2%vs 0·5 ± 2·9%, P < 0·05). Conclusion Calcium supplementation appears to affect femoral bone mass less in Thai postmenopausal women with adequate vitamin D status, despite higher suppression of PTH.     

Bone mineral density and bone turnover in relation to serum leptin, α-ketoglutarate and sex steroids in overweight and obese postmenopausal women

Objective Recent studies have shown that parallel changes in body weight and bone mass can be partially mediated via circulating leptin. Therefore, among the hormones involved in bone and mineral metabolism, such as oestrogens, testosterone and parathormone, leptin has recently become a subject of considerable interest. The aim of this study was to assess associations between leptin, E₂, testosterone, dehydroepiandrosterone sulphate (DHEA‐S), SHBG, α‐ketoglutaric acid (AKG) and bone mineral density (BMD) and bone turnover markers in overweight and obese postmenopausal women. Design Eighty healthy, postmenopausal Caucasian women were studied. BMD of the lumbar spine (L₂–L₄) and femoral neck regions were examined using the dual X‐ray absorptiometry (DXA) method. Associations were evaluated in stepwise multiple regression analysis, including information on the possible confounders and effect modifiers, for example, age, years since menopause, height and weight. Results Femoral neck BMD was positively correlated with weight (r = 0·52, P < 0·000001), body mass index (BMI) (r = 0·48, P < 0·000006), hipline (r = 0·48, P < 0·00006), waistline (r = 0·45, P < 0·00002) and DHEA‐S (r = 0·36, P < 0·0008). Correlations of E₂, SHBG, testosterone and leptin, as well as biochemical markers of bone turnover with L₂–L₄ and femoral neck BMD were not found. In the whole study group, significant predictors of L₂–L₄ BMD were BMI (β = 0·35, P < 0·01) testosterone (β = 0·27, P < 0·05) and osteocalcin (OC) (β = 0·22, P < 0·05) (R² = 0·23), while predictors of femoral neck BMD were BMI (β = 0·42, P < 0·001), testosterone (β = 0·24, P < 0·05), E₂ (β = 0·19, P < 0·05), as well as osteocalcin (β = 0·20, P < 0·05) (R² = 0·41). In the subgroup with BMI 30–39·9, the significant predictors of both L₂–L₄ and femoral neck BMD were testosterone (β = 0·32, P < 0·05, R² = 0·19; β = 0·33, P < 0·05, R² = 0·29) and osteocalcin (β = 0·34, P < 0·05, R² = 0·19; β = 0·45, P < 0·01, R² = 0·29). In the subgroup with waist : hip ratio (WHR ≥ 0·85, the predictor of L₂–L₄ BMD was E₂ (β = 0·38, P < 0·05) (R² = 0·21), whereas the predictors of femoral neck BMD were BMI (β = 0·29, P < 0·05) and testosterone (β = 0·35, P < 0·01) (R² = 0·36). Conclusion The main endocrine variable predicting lumbar spine BMD in overweight and obese postmenopausal females was testosterone, while the main determinants of femoral neck BMD were both testosterone and E₂. No effect was found of serum leptin on examined indicators of bone status.     

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts

Background

Subclinical hyperthyroidism (SH yper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear.

Objective

To investigate the association between subclinical thyroid dysfunction and bone loss.

Methods

Individual participant data analysis was performed after a systematic literature search in MEDLINE /EMBASE (1946–2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD ) measurements. We classified thyroid status as euthyroidism (thyroid‐stimulating hormone [TSH ] 0.45–4.49 mIU/L), SH yper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SH ypo, TSH ≥ 4.50–19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X‐ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random‐effects two‐step approach.

Results

Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SH ypo and 284 (5.2%) had SH yper. During 36 569 person‐years of follow‐up, those with SH yper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = ?0.18 (95% CI: ?0.34, ?0.02; I ² = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = ?0.14 (95% CI: ?0.38, 0.10; I ² = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: ?0.30, 0.36; I ² = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = ?0.59; [95% CI: ?0.99, ?0.19]) and total hip region (%ΔBMD = ?0.46 [95% CI: ?1.05, ?0.13]). In contrast, SH ypo was not associated with bone loss at any site.

Conclusion

Amongst adults, SH yper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

     

Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism

Background Primary hyperparathyroidism (PHPT) is associated with reduced bone mineral density (BMD) mainly at sites rich in cortical bone. However, successful parathyroidectomy causes an increase in BMD especially at sites rich in trabecular bone. Plasma 25‐hydroxyvitamin D (25OHD) levels are typically reduced and plasma 1,25‐dihydroxyvitamin D [1,25(OH)₂D] slightly increased in PHPT. These variations in vitamin D metabolites may influence variations in BMD and fracture risk. Aim To investigate relations between preoperative vitamin D metabolites and skeletal consequences in patients with untreated PHPT and to appraise the influence of preoperative vitamin D metabolites on postoperative changes in BMD. Design Cross‐sectional and cohort study. Materials Two hundred and forty‐six consecutive Caucasian PHPT patients aged 19–91 years. (median 63, 87% females). Results BMD was reduced at the femoral neck (P < 0·001) and forearm (P < 0·001), but normal at the lumbar spine (P = 0·11). Levels of biochemical bone markers were associated with high plasma PTH, high plasma 1,25(OH)₂D and low plasma levels of 25OHD. Moreover, low plasma 25OHD was associated with low levels of BMD at the femoral neck (r_p = 0·23), the forearm (r_p = 0·19) and the whole body (r_p = 0·30), whereas plasma 1,25(OH)₂D was inversely associated with BMD at all regional sites and the whole body. Plasma PTH only showed an inverse association with BMD at the forearm (r_p = –0·21). No association was observed between biochemical variables and prevalent spinal fractures, all peripheral fractures or osteoporotic peripheral fractures. The annual increase in spinal BMD after surgery was positively associated with preoperative plasma PTH (r_p = 0·40), whereas the annual increase in whole body BMD was inversely associated with plasma 25OHD (r_p = –0·32). No change in BMD at the femoral neck and forearm was observed 1 year after surgery. Conclusion Low vitamin D status and high plasma 1,25(OH)₂D are associated with increased bone turnover and decreased BMD in patients with PHPT.     

Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women

OBJECTIVE: Hyperthyroidism is accompanied by low bone mass. Because the reference range of TSH levels is defined statistically, some individuals with low normal TSH levels may have mild hyperthyroidism and reduced bone mass. We therefore determined whether serum TSH levels correlate with bone mineral density (BMD). DESIGN: A cross-sectional hospital-based survey. Participants Nine hundred and fifty-nine healthy postmenopausal women. MEASUREMENTS: We measured BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry, and serum TSH concentrations using immunoluminometry. RESULTS: BMD at the lumbar spine and femoral neck increased with TSH level (P for trend < 0.001 at both sites). Even after adjustment for age, years since menopause and body mass index, subjects with low normal TSH levels (0.5-1.1 mU/l) had significantly lower BMDs at the lumbar spine (0.863 +/- 0.009 g/cm2 vs 0.900 +/- 0.009 g/cm2, P = 0.004) and femoral neck (0.660 +/- 0.006 g/cm2 vs 0.683 +/- 0.006 g/cm2, P = 0.006) than those with high normal TSH levels (2.8-5.0 mU/l), as well as a 2.2-fold increased risk of osteoporosis (95% confidence interval: 1.2-4.0). CONCLUSION: These results suggest that low normal TSH levels may not be physiological for postmenopausal women and, during treatment of hypothyroidism, may not be adequate for avoiding osteoporosis.     

Lean mass and fat mass predict bone mineral density in middle-aged individuals with noninsulin-requiring type 2 diabetes mellitus

Objective Despite high bone mineral density (BMD), persons with type 2 diabetes are at greater risk of fracture. The relationship between body composition and BMD in noninsulin‐requiring diabetes is unclear. The aim was to examine how fat and lean mass independently affect the skeleton in this population. Research design and methods Subjects for this cross‐sectional analysis were men (n = 78) and women (n = 56) aged 40–65 years (56 ± 6 years) with uncomplicated, noninsulin‐requiring type 2 diabetes. Total body fat and lean mass, total body, hip and lumbar spine BMD were measured with dual energy X‐ray absorptiometry. Magnetic resonance imaging measured total abdominal, visceral and subcutaneous (SQ) fat. Results Subjects had normal all‐site BMD and were obese to overweight (body mass index 29–41 kg/m²) with controlled diabetes (HbA1c women 6·6 ± 1·2%, men 6·7 ± 1·6%). Lean mass was positively associated with total body, hip, femoral neck and hip BMD in both sexes. Fat mass, abdominal total and SQ fat were associated with total body and hip BMD in women. In multivariate analyses adjusted for sex, lean mass significantly predicted total, hip and femoral neck BMD in men and women. In unadjusted models, lean mass continued to predict BMD at these sites in men; fat mass also predicted total body, femoral and hip BMD in women. Conclusions In men and women with uncomplicated, noninsulin‐requiring diabetes, lean mass significantly predicted BMD at the total body, hip and femoral neck. Further research is needed to determine whether acquisition or maintenance of lean mass in T2DM can prevent hip fracture in this at‐risk population.     

The relationship between gonadotrophins, gonadal hormones and bone mass in men

Objective Inhibin A and B (Inh A and B), activin A (Act A) as well as FSH may play an important role in bone turnover in perimenopausal women. Data in men are lacking. The aim was to investigate the relationship between circulating concentrations of Inh B and Act A and FSH/LH/testosterone (T) and their contribution to bone mineral density (BMD) in a male population. Design and subjects Cross‐sectional case‐control study of 156 men, 63 with osteoporosis and 93 controls, aged (mean [SD]) 57·7 [13·7] years. Measurements Areal (aBMD) was measured at the femoral neck, total hip and lumbar spine. Volumetric BMD (vBMD) was calculated at the femoral neck and lumbar spine. Risk factors were assessed including the measurement of LH/FSH/T, Inh B and Act A. Results After correction for age and body mass index (BMI), associations were found between Inh B and FSH (beta regression coefficient β = ?0·326; P < 0·0001), T (β = ?0·36; P = 0·019) and Act A (β = ?0·4; P = 0·007) and between Inh B and LH (β = 0·23; P < 0·0001) in all patients. The controls had higher Inh B concentrations compared to the cases (Inh B: controls: 139 [86] pg/ml vs. cases 88 [51] pg/ml; P = 0·005). Act A tended to be lower in the controls (Act A: controls 0·63 [0·24] ng/ml vs. cases 0·75 [0·4] ng/ml; P = 0·056). Univariate regression analyses showed a positive association between Inh B and BMD (P < 0·01) at the lumbar spine and total hip. In contrast a negative association was seen between FSH and BMD at the lumbar spine and femoral neck (P < 0·01). In a partial multivariate regression model that included the gonadal factors only, a positive association was seen between Inh B and BMD at the hip (β = 0·088; P = 0·04). When all hormones including the gonadotrophins were entered in a full multivariate model, FSH and LH were found to be better predictors of BMD than Inh B or Act A in the controls and cases. Conclusions These data suggest that the gonadal peptides and gonadotrophins may play a role in the maintenance of bone mass in men. Future confirmatory longitudinal studies are needed.     

Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency

OBJECTIVE Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency. DESIGN Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months. PATIENTS Twenty-two adults (10 men, 12 women), aged 41.5±2.1 years (mean ± SE, range 23.6–59.5), with adult onset GH deficiency. MEASUREMENTS Single-energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle Integral BMD. RESULTS After 6 months of GH replacement (n=21) there was a significant decrease In forearm cortical BMD (SPA: median change ?0.009g/cm², P=0.01), forearm Integral BMD (SPA: median change ?0.016g/cm², P=0.03), lumbar spine BMD (DXA: median change ?0.022g/cm²; P=0.003) and femoral neck BMD (DXA: median change ?0.029g/cm², P=0.006). After 12 months of GH replacement (n=13) there was a significant decrease in lumbar spine BMD (DXA: median change ?0.035 g/cm², P=0.002) from baseline. There was no significant Increase in bone mass at any site after 6 or 12 months of GH replacement. Change In bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies. CONCLUSION The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer-term studies are required to determine whether prolonged GH replacement has a beneficial effect on bone mass.     

Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor

Objective To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR). Design and patients The Longitudinal Ageing Study Amsterdam (LASA), a population‐based cohort study in older men and women. Measurements Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X‐ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self‐report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BclI) were genotyped by Taqman (n = 858). Results Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = –0·135, P = 0·04). No significant associations in men were found. Female 9beta G‐allele carriers had 50·2 nmol/l lower cortisol and 1·2 lower free cortisol levels than AA homozygotes [P = 0·01 for (free) cortisol]. Furthermore, female BclI GG homozygotes had 54·8 nmol/l higher cortisol levels than C‐carriers (P = 0·03). In the total population, BclI GG homozygotes had 0·05 g/cm² lower trochanteric region BMD (P = 0·03). For the other GR gene polymorphisms, no significant associations were found. Conclusions Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BclI GG homozygotes had higher serum cortisol levels, and BclI GG homozygotes had lower trochanteric region BMD in the total population.     

Analysis of factors associated with the lumbar spine and proximal femur bone mineral density in coal miners: a cross-sectional survey

Background

Chinese coal miners are at high risk of occupational disease becausethey work underground during most of the daylight hours and are exposed to weight-bearing activity. But data concerning bone mineral density (BMD) and risk factors of BMD is lacking. We aim to identify the factors associated with low bone BMD in coal miners.

Changes in bone mass and metabolism after surgery for primary hyperparathyroidism

BACKGROUND AND OBJECTIVE Bone mass Is often reduced In patients with primary hyperparathyroidism (pHPT) and Is usually partially reversible after parathyroidectomy. However, site specific and overall skeletal benefits of surgery in mild asymptomatic pHPT remain uncertain. DESIGN Cross-sectional and longitudinal studies. PATIENTS Fourteen patients (12 women and 2 men) with pHPT. MEASUREMENTS Baseline bone mass was assessed at the lumbar spine, left hip and whole body using dual-energy X-ray absorptiometry, and at the left os calcls using broad-band ultrasound attenuation. Changes in bone mass, serum Intact PTH and osteocalcin, and urinary pyrldlnium cross-link excretion were recorded In 10 patients followed for 6 months after surgery. RESULTS (1) Cross-sectional study: Baseline measurements at the lumbar spine and hip were Inversely related to both the serum PTH concentration and the weight of the parathyroid gland removed at surgery. (2) Longitudinal study: Six months after adenectomy, bone mass had Increased significantly at the femoral neck, greater trochanter, whole body and os calcis, but not at the lumbar spine or Ward's area. Serum PTH, osteocalcin and pyrldlnium cross-link excretion all fell significantly after surgery. The percentage Increment In whole body bone mineral content at 6 months was proportional to the baseline PTH. CONCLUSION In primary hyperparathyroidism, preoperative reductions and post-operative gains in bone mass are proportional to the Initial serum PTH concentration. Mild primary hyperparathyroidism probably does not cause appreciable bone loss at clinically relevant fracture sites such as the spine and hip, and In such cases the overall skeletal benefits of surgery are likely to be negligible.     

Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation

OBJECTIVE Our clinical practice has been to offer treatment with cyclical disodlum etidronate and high dose calcium supplements (1500–1600 mg/day) to ail female patients with osteoporosis who are unable or unwilling to take hormone replacement therapy (HRT), and male osteoporotics. In a retrospective study we compared the effect of this treatment on measures of bone mineral over a 12-month period in women wlth post-menopausal and secondary osteoporosis. We also assessed its effects in 10 male osteoporotics. DESIGN A retrospective analysis of 83 consecutive patients with osteoporosis who completed 12 months of treatment with disodlum etldronate and calcium and who had a dual energy X-ray absorptiometry (DEXA) scan at baseline and foilowing 12 months of therapy. PATIENTS The study Included 73 women (45 post-meno-pausal and 28 secondary osteoporotics) and 10 men with established osteoporosis as shown by spinal and femoral bone mineral densities (BMD) > 2 standard deviations (SD) below young normals, and radioiogical evidence of osteoporosis. MEASUREMENTS Each patient had routine biochemistry at baseline, an X-ray of thoracic and lumbar spine and a DEXA scan of lumbar spine (L2-L4) and femoral neck. The DEXA scan was repeated following 12 months of therapy. RESULTS There was no difference between increase in spinal BMD in the post-menopausal (5·7%) versus secondary osteoporotic group (6·7%). There was a significant increase in spinal BMD at 12 months in the 10 male osteoporotics (9·0%, P < 0·01). No overall change in femoral neck BMD was noted. CONCLUSIONS Cyclical disodium etidronate given with hlgh dose calcium supplements is equally effective in increasing spinal bone mineral density in post-menopausal and secondary osteoporosis. It also results in a significant rise In spinal bone mineral density in male osteoporotics. Whether this produces a reduction in fracture rates is unknown.