Importance of bioavailable calcium drinking water for the maintenance of bone mass in post-menopausal women

The aim of this research was to establish the importance of calcium intake through mineral water on vertebral bone density in women. To this purpose, we examined 255 women divided into two groups: those regularly drinking a high calcium content mineral water (group A; no.=175) and those using different type of water with a lower calcium content (group B; no.=80). Their dietary daily calcium intake was determined by means of a validated questionnaire (N.I.H. Consensus statement) and vertebral bone density was measured by Dual-Energy X-ray absorptiometry (Unigamma-plus ACN densitometer). Women in group A ingested a significantly higher quantity of calcium in water than women in group B (mean difference 258 mg; 95% confidence limits: 147-370 mg). The average bone density values were slightly but significantly higher in group A as compared to group B (mean+/-SD: 1.044+0,15 vs 1.002+0,14; p=0.03). In addition to age, BMI and menopausal status, calcium intake was a significant predictor of spinal BMD. These 4 variables explained about 35% of the spinal BMD variance. When the analysis was repeated separately for pre- and post-menopausal subjects, calcium remained a significant predictor in post-menopausal women (t=2.28; p=0.02), but not in premenopausal women. These results underline the importance of a lifelong daily calcium intake, resulting by the regular drinking of high bioavailable calcium water, in order to maintain bone mass after the menopause, in comparison to the use of a lower content calcium water.     

Body composition and bone mass in post-menopausal women

OBJECTIVE: We aimed to assess total body composition and to study the interrelationships between fat and lean tissue mass with total and regional bone mass in healthy British post-menopausal women. DESIGN AND PATIENTS: Total body composition and regional bone mass were measured in 97 healthy post-menopausal women recruited from the general community. The mean age was 57.9 years, range 49-65. MEASUREMENTS: Total body composition (fat, lean tissue and bone mineral) and regional bone density in the lumbar spine and femur were measured by dual energy X-ray absorptiometry on a Lunar DPX. RESULTS: Significant negative correlations with age were found for total body bone mineral density (r = -0.200, P = 0.049), and lumbar spine bone mineral density (r = -0.28, P = 0.006); the calculated rate of bone loss from these two sites was 0.33 and 0.7% per annum respectively. Fat tissue mass showed a positive correlation with age (r = 0.22, P = 0.03). High correlations were observed between total body and regional bone mineral density (r = 0.755-0.829, P < 0.001). After adjustment for age and lean mass, statistically significant correlations were seen between fat tissue mass and all bone mass measurements (P < 0.01-0.001), the strongest correlations being found for total body bone mineral content and density (r = 0.477 and 0.488 respectively). Lean tissue mass showed a strong correlation with total body bone mineral content (r = 0.580, P < 0.001), after adjustment for age and fat mass; it was less strongly correlated with other bone mass measurements than fat mass, showing only weak correlations with total body, trochanteric and lumbar spine bone mineral density (r = 0.228-0.246, P < 0.05). Age-adjusted body weight showed stronger correlations with total and regional bone mass than did either body mass index or height. CONCLUSIONS: Both fat and lean tissue mass are related to total and regional bone mass in post-menopausal women, the relationship being strongest for fat mass. Body weight shows stronger correlations with bone mass than either height or body mass index. In view of the direction and magnitude of changes in fat, lean tissue and bone mineral after the menopause, adiposity and muscularity are more likely to be determinants of peak bone mass than of the rate of post-menopausal bone loss.     

Effects of norethisterone on bone related biochemical variables and forearm bone mineral in post-menopausal osteoporosis

OBJECTIVE Progestogens may be a useful therapeutic alternative to oestrogen in the treatment of post-menopausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patients with post-menopausal osteoporosis. DESIGN/PATIENTS The effects of treatment with norethisterone (5 mg/day) on bone related biochemical variables was determined in 44 women with post-menopausal osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC) were evaluated by serial measurements in 39 of these women. MEASUREMENTS We measured forearm mineral content, forearm mineral density, forearm fat content and fat-corrected forearm mineral density. Biochemical measurements included plasma calcium and plasma calcium fractions (ionized, protein bound, complexed and ultrafiltr-able), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid hormone, osteocalcin and 1,25-dihydroxyvitamin D, radiocalcium (⁴⁵Ca) absorption and fasting urinary calcium/creatinine, sodium/creatinine, phosphate/creatinine and hydroxypro-line/creatinine molar ratios. RESULTS After 4 months of treatment norethisterone produced a fall in plasma calcium (mean ± SEM from 2 40 ± 0 14 to 2 32 ± 0 13 mmol/l, P < 0 001), primarily in the non-ionized calcium, due to a decrease in plasma bicarbonate (from 29 ± 0–28 to 27 ± 0–28 mmol/l, P < 0 001). There were decreases in urinary calcium/creatinine (from 0 41 ± 0 03 to 019 ± 0 02, P < 001) and sodium/creatinine (from 15 ± 11to10 ± 0 93, P< 0 001) molar ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa) (from 2 36 ± 0 041 to 2 55 ± 0 059 mmol/l of glomerular filtrate, P < 0 001). Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate reabsorption (TMP) all fell (P<001). Both the urinary hydroxyproline/creatinine (P < 0 001) and plasma alkaline phosphatase (P < 0 001) fell. Serum parathyroid hormone rose from 41 ±0 36 to 5-5 ±0–51 pmol/l (P < 0 02) and radiocalcium absorption increased from 0 67 ±0 08 to 0 81 ±0 10 fx/h (P < 0 01). There was no change in serum 1,25-dihydroxy vitamin D. After treatment with norethisterone for 4 months there was an increase in forearm bone mineral content (P<0 05) and a decrease in forearm fat content (P < 002). After two years treatment with norethisterone fat-corrected forearm bone mineral content rose (mean change 17-0 ± 5-5 mg/cm, P < 0 01). CONCLUSIONS These results suggest that norethisterone prevents bone loss in post-menopausal osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on intestinal calcium absorption, and increases serum parathyroid hormone levels.     

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.     

Whole body composition and regional bone mass in women with insulin-dependent diabetes mellitus

OBJECTIVE Reduced bone mass has been reported In adult patients with insulin-dependent diabetes mellitus but there are few data on bone density in the axial skeleton or on whole body composition In this group. The aim of this study was to determine whether whole body and regional bone mass are normal in middle-aged women with insulin-dependent diabetes mellitus. DESIGN Total and regional bone mass were measured In 24 post-menopausal women aged 43–69 years (mean 56·3) with insulin-dependent diabetes, recruited during routine clinic attendance. Results were compared with those obtained from 24 age and weight-matched community-based post-menopausal women. MEASUREMENTS Whole body bone mineral Content and bone mass in the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry on a Lunar DPX. RESULTS Whole body bone mineral content was significantly lower in the diabetic women than in community-based controls (P= 0·02). There was no significant difference between the two groups in whole body bone density or lumbar spine bone density. Mean bone density in the femur was lower in the patient group at all sites assessed (femoral trochanter P= 0·003, femoral neck, P= 0·057). Values for all regional bone density measurements in the diabetic women were within the Lunar reference range (mean ± 2 SD) and at all sites the mean value was close to 100% of the sex and age-matched reference value. There was no correlation between duration or control of diabetes and bone mass at any site. CONCLUSIONS Insulin-dependent diabetes mellitus In middle-aged women is associated with small reductions in total body bone mineral content and in femoral bone density; the clinical Significance of these findings in terms of subsequent fracture risk remains to be established. No evidence was found In this study for a reduction in whole body or lumbar spine bone density.     

Continuous combined oestrogen/progestin therapy is well tolerated and increases bone density at the hip and spine in post-menopausal osteoporosis

OBJECTIVES Although oestrogen/progestin therapy is effective prophylaxis against post-menopausal osteoporosis, its efficacy in the treatment of established disease is uncertain. In addition, cyclical oestrogen/progestin regimens are associated with low rates of patient acceptance. The present study assesses the acceptability of, and skeletal response to, continuous combined hormone replacement therapy in osteoporotic late post-menopausal women. DESIGN Retrospective, controlled study. PATIENTS One hundred and four osteoporotic late postmenopausal women treated with continuous combined hormone replacement therapy (5 mg medroxyprogester-one acetate daily and either 0·625 mg oral conjugated oestrogens or 50 μg transdermal oestradiol daily) were followed for an average of 1 year (range 2–38 months). Control subjects were 19 healthy normal women matched for menopausal age and weight. MEASUREMENTS Adverse effects and compliance rate were monitored. Baseline and 1-year measurements of lumbar spine bone mineral density (BMD) were performed using dual-energy X-ray absorptiometry in 51 women, 22 of whom also had measurements at 2 years. Twenty-eight women had proximal femur scans at baseline and 1 year. RESULTS Eighty-six per cent of women continued to take continuous combined hormone replacement therapy at the end of follow-up. Mastalgia (44%) and vaginal bleeding (29%), the most common side-effects, were minor and self-limiting in virtually all women. Spinal BMD increased by 7·1 ± 0·8% (mean±SEM P < 0·001) at 1 year and by 8·9 ± 1·5% (P < 0·001) at 2 years. In the proximal femur, BMD increased by 2·9 ± 0·9% at the femoral neck (P= 0·01) and by 2·5±0·9% (P= 0·001) at the trochanter at 1 year. BMD tended to decline in the control group. Among the women taking hormone replacement therapy, the increase in spinal BMD was similar in those treated with 0·3–0·44 mg/day of conjugated equine oestrogens to those receiving 0·45–0·625 mg/day. CONCLUSION Continuous combined hormone replacement therapy is an acceptable therapy to osteoporotic late post-menopausal women and produces substantial increases in lumbar spine and proximal femoral bone mineral density.     

Short-term Administration of Glucagon-like Peptide-2. Effects on Bone Mineral Density and Markers of Bone Turnover in Short-Bowel Patients with No Colon

Background: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of shortbowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. Methods: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 μg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. Results: Mean ± s x (SEM) percent changes in spinal and hip BMD were 1.1 ± 0.4% ( P < 0.05) and 1.9 ± 0.8% ( P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% ( P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. Conclusion: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.     

Effect of long-term administration of progestogen on post-menopausal bone loss: result of a two-year, controlled randomized study

OBJECTIVE We determined whether a progestogen given alone to post-menopausal women may prevent bone loss. STUDY DESIGN Thirty-five early post-menopausal women who had not received any form of treatment to prevent bone loss were randomly assigned to a 2-year regimen of 500 μ g/day of a gestagen derived from 19-norprogester-one (Promegestone) or a placebo for 21 days out of a 28-day treatment cycle. Bone mineral density of the spine was measured by dual photon absorptiometry. RESULTS After 2 years of treatment bone mineral density decreased significantly in the placebo group by a mean of 4.5%. In the gestagen group, the rate of bone change was significantly lower as compared to the placebo group (-1.3%± 1.2% vs ?4.5%± 2% (mean ± SEM), P & lt; 0.05). There were no changes in the biochemical bone turnover parameters in the placebo group but in the gestagen group a significant decrease was observed in the urinary calcium excretion after 2 years. CONCLUSION The results suggest that a gestagen with no androgenic action can partly counteract early post-menopausal bone loss.     

Effect of progestin therapy on cortical and trabecular bone: comparison with estrogen.

PURPOSE: To determine the effect of progestin therapy on bone mineral density in postmenopausal women and to compare its effects to those of estrogen. SUBJECTS AND METHODS: A prospective, randomized clinical trial was performed in 81 postmenopausal women aged 51.7 +/- 4.4 years (mean +/- SD). They were assigned to one of four groups: Provera 20 mg, Premarin 0.6 mg, Premarin 0.3 mg plus Provera 10 mg, and a placebo. In addition, all women received calcium supplementation, if necessary, to a calcium intake of 1,000 mg/day. We used single- and dual-photon absorpiometry, metacarpal radiogrammetry, and computed axial tomography to measure bone mineral density in the total skeleton, spine, radius, and metacarpal. RESULTS: Women receiving placebo lost bone at all sites (p less than 0.01). The Provera-treated group showed no change in total body calcium, but there were decreases in radial density (p less than 0.01), metacarpal cortex (p less than 0.01), and spine density (p less than 0.01). The Premarin-treated group had an increase in spine density and total body density (p less than 0.05), but a decrease in radial density (p less than 0.05). The Premarin-plus-Provera group showed no change in spine density, total body calcium, or radial density but had a decrease in metacarpal cortex (p less than 0.01). CONCLUSIONS: Compared to placebo, Provera reduced the rate of loss in cortical areas of the skeleton, but not in the spine, which contains more trabecular bone. In contrast, Premarin reduced the rate of loss in both cortical and trabecular areas of the skeleton. The low-dose combination of Premarin plus Provera was similar in its effect on bone to that of Premarin alone, suggesting that there may be a synergistic effect of this hormone combination on bone. Serum cholesterol levels decreased with Provera, Premarin, and the combination of both, whereas levels of serum triglycerides increased with Premarin treatment, decreased with the Provera regimen, and were unchanged with the combination therapy. Provera does not adversely affect the lipid profile.     

THE EFFECTS OF NAFARELIN AND DANAZOL ON VERTEBRAL TRABECULAR BONE MASS IN PATIENTS WITH ENDOMETRIOSIS

Single and dual-energy quantitative computed tomography (QCT) were used to measure spinal trabecular bone mineral content in 24 women treated with either nafarelin (15 patients) or danazol (nine patients) for endometriosis. Significant loss of bone mineral (-9.6 g/l; -5.9% P less than 0.001) was demonstrated after 6 months' treatment with nafarelin. This loss was reversible with no significant difference in the bone mineral measurement made before treatment and that made at 6 months after treatment was stopped (difference -1.95 g/l, NS). A small but statistically significant (+2.2 g/l, P less than 0.05) increase in bone mineral was measured in the group of patients treated with danazol for 6 months. The dual-energy QCT gave similar results, indicating little change in trabecular fat content. A significant correlation was demonstrated between mean serum oestradiol levels during treatment with nafarelin and the change in bone mineral (r = 0.655, P less than 0.005).     

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism*

OBJECTIVE The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with blosynthetic human GH in hypopituitary adults on aspects of calcium homeostatis, bone metabolism and bone mineral mass. PATIENTS Forty hypopituitary adults (21 females and 19 males; aged 19–67 years). DESIGN A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL Following baseline assessments, GH was given in a daily dose of 0·02–0·05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I Increased significantly on GH treatment (mean ± SD) (GH: 276 ± 197 vs P: 88 ± 50 μg/l, P < 0 0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2·23 ± 0·11–2·29 ± 0·11 mmol/l, P<0·05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2·29 ± 0·11; P, 2·26 ± 0·09 mmol/l). Plasma phosphate increased on GH (GH: 1·02±0·23–1·32±0·19; P: 0·99±0·16–0·96±0·12 mmol/l over the 6 months of treatment, P<0·001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104±32 vs P: 69±32 U/I, P<0·01, osteocalcin: GH: 17·2±8·0 vs P: 5·3±3·2 μg/l, P<0·001 and P1CP: GH: 207 ± 152 vs P: 93±31 μg/l, P<0·01). There was no difference in the intact parathyroid hormone level (GH: 31 ± 14 vs P:31 ± 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.     

Diagnostic approach to osteoporosis and spondyloarthrosis in post-menopausal women by total body dual-photon absorptiometry

Dual-photon absorptiometry of total body (153 Gd with photopeaks at 44 and 100 keV) enables bone mineral content of the entire skeleton and its major anatomical areas to be quantitated. Total body bone mineral (TBBM), total body density (TBD), bone mineral content and bone density of spine and lumbar-spine were measured in 97 women with post-menopausal osteoporosis, 33 females with spondyloarthrosis and in 19 females with spondyloarthrosis associated with osteoporosis. Seventy-nine females of similar age made up the normal control group. TBBM and TBD proved to be significantly lower in post-menopausal osteoporotic women compared to age-matched normal females: bone loss was particularly evident in spine measurements. In spondyloarthrosis patients TBBM and TBD fell within the normal range and both spine bone density and spine bone mineral did not differ from normals. TBD, TBBM, spine density and spine mineral in females with disuse osteoporosis associated with spondyloarthrosis were significantly lower in comparison with normals and higher with respect to post-menopausal osteoporotic women. Total body absorptiometry represents a valuable method in the differential diagnosis of post-menopausal osteoporosis, spondyloarthrosis and the disuse osteoporosis associated with spondyloarthrosis.     

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.     

Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls

Objective

Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM.

Methods

An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 μm³ voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x‐ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up‐and‐go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI).

Results

Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups.

Conclusion

In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population.     

Melatonin increases oestradiol-induced bone formation in ovariectomized rats

To assess the effect of melatonin on bone metabolism in ovariectomized rats, receiving oestradiol therapy or not, melatonin was administered in the drinking water (25 microg/mL water) and oestradiol (10 microg/kg body weight) or vehicle was given subcutaneously 5 days/week for up to 60 days after surgery. Urinary deoxypyridinoline (a marker of bone resorption) and circulating levels of bone alkaline phosphatase activity (a marker of bone formation), as well as serum calcium and phosphorus levels, were measured every 15 days. Bone area (BA), bone mineral content (BMC), bone mineral density (BMD) and total body fat (expressed as 100 g body weight) were measured by dual-energy X-ray absorptiometry at the end of the experiment. Body weight and total body fat were augmented after ovariectomy, and decreased after melatonin or oestradiol treatment. The effect of melatonin on body weight was seen in sham-operated rats only. Ovariectomy augmented, and melatonin or oestradiol lowered, urinary deoxypyridinoline excretion. This effect of melatonin and oestradiol was seen mainly in ovariectomized rats. The efficacy of oestradiol to counteract ovariectomy-induced bone resorption was increased by melatonin. Melatonin or oestradiol lowered serum bone alkaline phosphatase activity. Melatonin inhibition was seen mainly on the increase of bone alkaline phosphatase activity that followed ovariectomy. Serum phosphorus levels decreased after melatonin administration and were augmented after oestradiol injection; overall, melatonin impaired the increase of serum phosphorus caused by oestradiol. Ovariectomy decreased, and oestradiol increased, serum calcium levels while melatonin augmented serum calcium in sham-operated rats only. On day 60 after surgery, BMD and content decreased after ovariectomy and were increased after oestradiol injection. Melatonin augmented BA of spine and BMC of whole of the skeleton and tibia. The highest values observed were those of rats treated concurrently with oestradiol and melatonin. The present results indicate that: (i) melatonin treatment restrained bone remodelling after ovariectomy; (ii) the effect of melatonin required adequate concentrations of oestradiol; (iii) melatonin augmented oestradiol effects on bone in ovariectomized rats; (iv) a counter-regulation by melatonin of the increase in body fat caused by ovariectomy was uncovered. The melatonin doses employed were pharmacological in terms of circulating melatonin levels but not necessarily for some other fluids or tissues.     

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.     

Bone mineral content and density in asymptomatic children with coeliac disease on a gluten-free diet

OBJECTIVES: Osteoporosis is a complication of coeliac disease. A gluten-free diet improves but does not normalize bone mineral density in adult patients. Only limited data are available regarding the influence of the disease and diet on bone mineralization in children. The aim of this study was to evaluate the radial bone mineral content and density in children and adolescents who are asymptomatic on a gluten-free diet. SUBJECTS AND METHODS: The bone mineral content (BMC) and density (BMD) values of the non-dominant radius midshaft in 91 children (53 girls, 38 boys, mean age 11.7 years, mean duration of disease 8.7 years) were determined by single-photon absorptiometry. At the diagnosis and at least three years after commencement of a gluten-free diet, serum calcium, phosphorus, albumin concentrations and alkaline phosphatase activities were measured in all patients, and intact parathormone concentrations in 16 patients. RESULTS: The mean BMC Z-score value in the female adolescent group only was significantly lower than normal (mean Z-score -1.04, P < 0.01). In contrast, the mean BMD Z-score was significantly higher compared to a healthy population both in girls (mean Z-score +1.36, P < 0.001) and in boys (mean Z-score +0.53, P < 0.02), as well as in the total patient group (mean Z-score +1.01, P < 0.001). The radial diameter was significantly smaller than normal in both pre-pubertal and adolescent groups. Serum laboratory parameters of asymptomatic patients were in the normal range. The parathormone mean value was significantly lower after at least three years of gluten-free diet than at diagnosis (mean +/- SD 3.77 +/- 1.07 versus 7.89 +/- 2.54 pmol/l, P < 0.01), but significantly higher compared to controls (2.89 +/- 0.90 pmol/l, P < 0.05). CONCLUSIONS: These data indicate that treated, asymptomatic coeliac children and adolescents have normal or even higher radius mineral density values than controls, but the bone size remains reduced. Although there is no direct evidence of calcium malabsorption in this cohort of coeliac patients, the slightly higher parathormone levels, together with some other factors, particularly delayed puberty, may result in reduced bone size.     

Relationship between total and regional bone mineral density and menopausal state, body composition and life style factors in overweight Japanese women.

OBJECTIVE: To investigate whether menopausal state, body composition and lifestyle factors influence total and regional bone mineral density in overweight Japanese women. DESIGN: Cross-sectional study of women who were recruited to the weight reduction program held at community-based health promotion center in Tokyo area. SUBJECTS: A total of 178 women with a mean age of 48 y old (20-69 y) with a clear menstrual history and BMI over 24. MEASUREMENTS: Total, regional and lumbar spine bone mineral density (BMD) and body composition were measured using DXA (Lunar). Menstrual history was taken by a questionnaire and walking steps per day and energy intake were measured. Physical fitness was assessed by cardio-respiratory fitness and leg extension power. Subjects were divided into pre-menopausal and post-menopausal groups. RESULTS: Pre-menopausal group had significantly higher total body BMD as well as regional BMD than post-menopausal group. However, no differences in BMI, percentage fat and fat mass (FM) were seen between the two groups. The multiple regression analysis stepwise method revealed that total and regional BMD correlated with menopausal state and total FM independently. Total and regional BMD did not correlate with total non-fat soft tissue mass (NFSM), energy intake, walking steps or physical fitness levels. Trunk and lower extremities BMD correlated with corresponding regional FM and NFSM, and upper extremities BMD correlated with only corresponding body part NFSM after adjusting menopausal state. CONCLUSION: Total and regional BMD had strong negative correlation with menopausal state rather than total FM in overweight Japanese women. Weight-bearing site BMD correlated with corresponding body part FM and NFSM and non-weight bearing site BMD only correlated with corresponding body part NFSM after adjusting for menopausal state.     

Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post-menopausal ages

OBJECTIVES We wished to appraise the effectiveness of hormone replacement therapy (HRT) in early (<67 years) and late (>67 years) post-menopausal women referred to a metabolic outpatient clinic for assessment of their bone status. Because older women often experience side-effects with conventional HRT, a low dose preparation (Estraderm 25) was also compared with conventional HRT (Estraderm 50). DESIGN AND SETTING Since all patients were symptomatic, the investigation was open and not placebo controlled. Patients were offered HRT and told about the two dosages. If they wished to use HRT, allocation of dosage was made randomly unless there were reasons to use a specific dose. PATIENTS One hundred and ninety-six women were studied over 1 or 2 years with 80 reaching 3 years of treatment. Patients were divided into those under 67 years and those over 67 years at the start of treatment. Each group was further divided into those taking Estraderm 25 and those taking Estraderm 50 with norethisterone if appropriate. MEASUREMENTS Bone mineral density (BMD) was measured (DXA, Hologic) at the lumbar spine and femoral neck at 0 year (196 patients), at 1 year (169 patients), at 2 years (139 patients) and at 3 years (80 patients). Patients losing bone were expressed as those whose 3 year BMD was lower than initial or as those whose BMD at 3 years had fallen by more than twice the coefficient of variation for that site (non-responders). RESULTS In lumbar spine, BMD increased maximally in the first year in all groups and the gain was maintained after 3 years. The change was similar whether patients were divided by age or dosage. For those on Estraderm 25, mean change after 3 years was 8.1 ± 6.8% and on Estraderm 50, 9.0 ± 8.3% (combined 8.7 ± 7.8%). Only 3.9% of patients were non-responders at the lumbar spine after 3 years. At femoral neck, changes were significant at 3 years only in the Estraderm 25 >67 years and Estraderm 50 <67 years groups and averaged 2.3 ± 5.4% for all patients. At the femoral neck, 10.4% of patients were non-responders after 3 years. Percentage change of BMD over 3 years at lumbar spine correlated with that at the femoral neck (r = 0.56). Percentage change of BMD at lumbar spine over 3 years correlated with menopausal age (r = 0.295). No relation was found between dosage of Estraderm/kg body weight and response of BMD at either site. CONCLUSIONS Transdermal oestrogen is effective at preventing bone loss in the spine at all post-menopausal ages and is capable of doing this in low dosage. Prevention of bone loss at the femoral neck is less certain and the average change in BMD over 3 years was significantly lower (P < 0.001) than in the lumbar spine. Use of Estraderm 50 is not associated with a greater response of bone mass and there was no evidence of an increasing BMD response as oestradiol dosage/kg body weight increased.