Recovery of bone density in women who stop using medroxyprogesterone acetate.
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Adult↗
Biomedical subjects
I R Reid
Publications and source records attributed to I R Reid.
Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal women.
We have previously found that fat mass but not lean body mass is related to bone mineral density (BMD) in women. In these and most other studies of the dependence of BMD on body composition, areal rather than volumetric bone density was measured. It is possible that the dependence of this variable on body size introduced a scale artifact that contributed to the previous findings. The present study addresses this issue by measuring the volumetric density of the third lumbar vertebra from simultaneous anteroposterior (AP) and lateral scans using dual-energy X-ray absorptiometry in 119 normal postmenopausal women. Whole body fat and lean body mass were also measured using this technique. In the AP projection, BMD was similarly related to body weight and to fat mass (r = 0.44, p < 0.0001 for both) but not to lean body mass (r = 0.17, NS). BMD in the lateral projection was less closely related to body composition than was AP BMD, but the greater impact of fat (r = 0.25, p < 0.01) than lean body mass (r = 0.09, NS) was still evident. When AP or lateral BMDs were divided by height, arm span or the square root of the scan area to produce an index with the dimensions of volumetric density, the dependence of BMD on body weight and fat mass was not affected but the relationship to lean body mass was eliminated (-0.02 < r < 0.09). Similarly, the volumetric density of the third lumbar vertebra was related to fat mass (r = 0.21, p = 0.02) but not to lean body mass (r = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
The investigation of hypercalcaemia.
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Humans↗
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 medroxyprogesterone acetate daily and either 0.625 mg oral conjugated oestrogens for 50 micrograms 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.
Adult↗
Determinants of the rate of bone loss in normal postmenopausal women.
Despite a large number of studies assessing relationships between putative risk factors and bone density, it is not known which factors influence the rate of axial bone loss in normal postmenopausal women. We have examined the relationships between the rate of bone loss (delta BMD) and variables related to calcium metabolism, lifestyle, diet (calcium, sodium, caffeine, and protein), body composition, muscle strength, sex hormones, and spinal osteophytosis in 122 normal postmenopausal women participating in a 2-yr prospective randomized placebo-controlled trial of calcium supplementation. Univariate correlation coefficients indicated that delta BMD at most sites was inversely related to baseline BMD and positively related to rate of change in body weight (0.10 < r < 0.36) and fat mass (0.11 < r < 0.42) during the study. Lean mass and its rate of change showed no consistent relationship to delta BMD. There was no correlation between delta BMD and any of the lifestyle, muscle strength, dietary, or hormonal indices or with the severity of spinal osteophytosis. Multiple regression analysis indicated that delta BMD in the total body was directly related to fat mass (P < 0.0001), the rate of change in fat mass (P < 0.0001), the renal tubular reabsorption of calcium (P < 0.01), and calcium treatment (P < 0.01) and inversely to the initial BMD (P < 0.0001; r2 = 0.42; P < 0.0001). Similar effects were seen throughout the skeleton, although the fraction of the variance accounted for was less in the subregions, consistent with the lower precision of measurement of regional bone density. It is concluded that baseline bone density, fat mass, and renal calcium handling are important factors influencing bone loss in normal postmenopausal women.
Body Composition↗
Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis.
There is a need for effective and acceptable therapies for postmenopausal osteoporosis. The bisphosphonates show promise in this role, but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported. We performed a 2-yr, randomized, double blind, placebo-controlled trial of pamidronate (150 mg/day) in 48 postmenopausal osteoporotic women. Bone mineral density of the total body, lumbar spine, and proximal femur was measured every 6 months by dual energy x-ray absorptiometry. Bone mineral density increased progressively in the total body (1.9 +/- 0.7%; P < 0.01), lumbar spine (7.0 +/- 1.0%; P < 0.0001), and femoral trochanter (5.4 +/- 1.3%; P < 0.001) in subjects receiving pamidronate, but did not change significantly in those receiving placebo. There were significant decreases in bone density at both the femoral neck (P < 0.02) and Ward's triangle (P < 0.01) in subjects taking placebo, which did not occur in the pamidronate group. The differences between the treatment groups were significant at all sites (0.0001 < P < 0.05) except Ward's triangle. Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo (P = 0.07), and there was a nonsignificant trend toward height loss being less in those receiving pamidronate (P = 0.16). It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis.
Aged↗
Benefits, risks and costs of calcium supplementation in postmenopausal women.
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Bone Density↗
Glucocorticoid osteoporosis.
Glucocorticoids act on calcium metabolism at many levels to produce osteoporosis, the major pathogenic effect probably being an inhibition of bone formation. In men, this is likely to be contributed to by a dose-related reduction in circulating testosterone concentrations. Bone density is reduced 10-20% at the commonly assessed sites, but deficits of twice this magnitude are found in trabecular bone. Dose and duration of steroid treatment influence the degree of osteopenia, but biochemical indexes of calcium metabolism are not predictive. In managing a steroid-treated patient, bone densitometry is usually helpful. Those with low densities should optimize their calcium intake, and those with sex hormone deficiency should receive appropriate replacement therapy. If bone loss is severe or continues despite these measures, the addition of bisphosphonate, calcitonin, fluoride, or a vitamin D metabolite may be appropriate, according to local availability. Thiazide diuretics can be combined with all these regimens. If thiazide diuretics are combined with vitamin D or its metabolites, careful monitoring of serum calcium should be undertaken. Bone density should be monitored annually until it is stable.
Administration, Inhalation↗
Effect of calcium supplementation on bone loss in postmenopausal women.
BACKGROUND: The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day. However, the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known. METHODS: We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day. The women were randomly assigned to treatment with either calcium (1000 mg per day) or placebo for two years. The bone mineral density of the total body, lumbar spine, and proximal femur was measured every six months by dual-energy x-ray absorptiometry. Serum and urine indexes of calcium metabolism were measured at base line and after 3, 12, and 24 months. RESULTS: The mean (+/- SE) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group (-0.0055 +/- 0.0010 g per square centimeter per year) as compared with the placebo group (-0.0097 +/- 0.0010 g per square centimeter per year, P = 0.005). The rate of loss of bone mineral density was reduced by 35 percent in the legs (P = 0.02), and loss was eliminated in the trunk (P = 0.04). Calcium use was of significant benefit in the lumbar spine (P = 0.04), and in Ward's triangle the rate of loss was reduced by 67 percent (P = 0.04). Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group. Serum parathyroid hormone concentrations tended to be lower in the calcium group, as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations. CONCLUSIONS: Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women.
Alkaline Phosphatase↗
Corticosteroid osteoporosis.
Glucocorticoids produce osteoporosis via a number of mechanisms, the most important of which is probably inhibition of bone formation. This results in reduction in bone mass of 10-20% at commonly assessed sites, but the bone loss is 30-40% when predominantly trabecular bone is measured. The dosage and duration of steroid treatment influence the extent of bone loss, but other factors are not predictive. At the present time, a patient who has demonstrable sex hormone deficiency should receive appropriate replacement therapy. Optimization of calcium intake is advisable. If bone loss is severe or continues in spite of these measures, the addition of a bisphosphonate, calcitonin, fluoride or a vitamin D metabolite may be appropriate, according to local availability. Thiazide diuretics can be combined with all of these regimens. If combined with vitamin D or its metabolites, careful monitoring of serum calcium levels should be undertaken. Bone density should be monitored annually until such time as it is stable.
Adrenal Cortex Hormones↗
Bone mineral density and body composition in adult patients with cystic fibrosis.
BACKGROUND: Cystic fibrosis is a multisystem disease characterised by chronic pulmonary sepsis and malnutrition. To ascertain whether osteoporosis is a feature of cystic fibrosis in adult patients, total body and regional bone mineral density (BMD) was measured in a group of eight men and eight women aged 17-42 years. METHODS: Total body and regional BMD (lumbar spine L2-L4, femoral neck, trochanteric, and Ward's triangle), as well as total body fat and lean mass, were measured by dual energy x ray absorptiometry. A range of biochemical, lifestyle, and anthropometric variables was also assessed. RESULTS: Patients with cystic fibrosis had significantly reduced bone density at all sites compared with normal young adults. The mean reductions ranged from 7% at Ward's triangle to 13% at the trochanter. Body mass index (BMI) was positively correlated with BMD at four sites and disease severity negatively correlated with BMD at two sites. Other biochemical and anthropometric variables were not predictive of bone density. Total body fat mass was reduced by 30% compared with normal young adults. CONCLUSIONS: Bone density is decreased in adult patients with cystic fibrosis and BMI and disease severity are independent predictors of bone density.
Adolescent↗
Circulating insulin levels are related to bone density in normal postmenopausal women.
We recently established that the dependence of bone mineral density (BMD) on body weight in women is mainly attributable to a close relationship between total body fat mass and BMD. The present study assesses whether this latter relationship might be contributed to by the hormones insulin or amylin, both of which may influence fat mass and calcium metabolism. Fifty-three normal postmenopausal women underwent a 75-g glucose tolerance test with measurement of plasma insulin and amylin concentrations every 30 min for 2 h. Body composition and BMD/height (to provide a quantity with the dimensions of volumetric density that is independent of body size) were measured by dual-energy X-ray absorptiometry, and volumetric density of the third lumbar vertebral body was calculated. Circulating insulin concentrations correlated with BMD/height and volumetric density of the third lumbar vertebral body (r = 0.28-0.52). They also were related to body weight (r = 0.34-0.56) and fat mass (r = 0.38-0.56) but were not independently related to lean mass on multiple regression. There were no consistent relationships between amylin levels and these variables. Multiple-regression analyses with fat mass and insulin levels as independent variables indicated that BMD/height of total body and femoral trochanter were primarily related to fat mass, whereas, in femoral neck, the significant relationship was with insulin. Volumetric density of the third lumbar vertebral body was related to insulin levels alone on this analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
The effect of leukemia inhibitory factor on bone in vivo.
The local effects of leukemia inhibitory factor (LIF) on bone turnover in vivo have been examined. Recombinant murine LIF (0.2 micrograms) or vehicle was injected daily for 5 days over the right hemicalvaria, and the mice were killed on day 6 or 13. Effects on calvarial bone morphology were assessed using quantitative histomorphometry of nondecalcified bone tissue. Increased bone resorption was present in LIF-treated hemicalvaria compared with that in the noninjected hemicalvaria or calvaria from mice injected with vehicle alone at both 6 and 13 days. Significant increases in LIF-treated animals were as follows. Eroded surface increased 10-fold (P = 0.022), osteoclast surface increased 5-fold (P = 0.003), osteoclast numbers increased 3-fold (P = 0.002), and the number of osteoclast nuclei increased 3-fold (P = 0.009). Fibrotic tissue was laid down in the resorption defects, and there was an accompanying thickening of the periosteum (3 times greater in LIF-injected animals; P = 0.003), causing the overall thickness of the treated bones to be almost doubled (P = 0.045). Indices of bone formation were increased in animals treated with LIF. Osteoblast numbers, osteoblast surface, and osteoid area were doubled (P = 0.012, 0.016, and 0.058, respectively). Similar effects of LIF were seen in indomethacin-treated animals. Small but statistically significant morphological changes were also seen in the left noninjected hemicalvariae when LIF-treated animals were compared to controls. LIF increased periosteal area (P = 0.01) and total mineralized bone area (P = 0.002). In conclusion, LIF accelerated bone turnover locally in a prostaglandin-independent manner in normal mice, demonstrating its potential to modify in vivo bone cell function dramatically.
Animals↗
Osteoporosis management.
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Estrogen Replacement Therapy↗
Leukaemia inhibitory factor and bone cell function.
A bone-resorbing product of mouse spleen cells found to have differentiation-inducing activity was most probably leukaemia inhibitory factor (LIF). This revealed that LIF is a cytokine active on bone, in addition to its several other sites of action. In organ culture of newborn mouse bone, recombinant LIF promoted bone resorption by a prostaglandin-dependent process. Resorption by isolated rat osteoclasts was also promoted by LIF through an initial action on osteoblasts which was receptor-mediated. Incorporation of [3H]thymidine into DNA was increased by LIF in cells (most probably osteoblasts) of the newborn mouse bones. Osteoblasts have been shown to produce LIF, and the amount is increased by treatment with retinoic acid or TNF-alpha. LIF also acts directly on osteoblasts to inhibit plasminogen activator activity, by stimulating the synthesis of plasminogen activator inhibitor 1 mRNA and protein. The latter actions are very similar to those of TGF-beta. Again like TGF-beta, LIF was ineffective in promoting bone resorption in vitro in fetal rat long bones. These results, together with the in vivo data showing that high circulating levels of LIF in the mouse are accompanied by a substantial increase in trabecular bone mass, indicate that LIF is another cytokine with potent actions on bone and potentially important interactions with other osteotrophic factors.
Animals↗
Lateral spine densitometry is a more sensitive indicator of glucocorticoid-induced bone loss.
Osteoporosis is a common complication of glucocorticoid therapy. Bone density measurement is now commonly used in assessing which steroid-treated patients require specific interventions to reduce fracture risk. The recently developed techniques for the measurement of bone mineral density (BMD) of the vertebral body alone, by dual-energy x-ray absorptiometry (DXA) in the lateral projection, may be particularly useful in this context since steroid-induced bone loss is most marked in trabecular-rich regions like the vertebral body. This possibility has been assessed in the present study by the measurement of BMD in the lateral and anterioposterior (AP) projections in 28 women receiving chronic glucocorticoid treatment. The two BMD measurements were significantly related (r = 0.62, p < 0.001). When expressed in relation to age-appropriate normal values, lateral BMDs were lower than AP BMDs both in percentage terms (70.8 +/- 4.4 versus 90.3 +/- 2.6%, p < 0.001) and in terms of Z scores (-1.42 +/- 0.22 versus -0.91 +/- 0.24, p = 0.027). AP BMD Z scores classified 12 patients as osteopenic, whereas a further 7 were so categorized by lateral BMD Z score. It is concluded that lateral DXA scanning is a more sensitive indicator of glucocorticoid-induced osteopenia than conventional BMD measurement in the AP projection.
Absorptiometry, Photon↗
Serum blocks the osteolytic effect of cortisol in neonatal mouse calvaria.
Chronic glucocorticoid excess is associated with the development of osteoporosis and, in human subjects, there is histomorphometric evidence of increased bone resorption. Paradoxically, most in vitro studies have suggested that glucocorticoids inhibit bone resorption but recently two groups have demonstrated increased osteolysis in glucocorticoid-treated bone organ cultures. The present study reexamines the effect of cortisol on basal bone resorption in neonatal mouse calvaria with particular emphasis on the effect of serum supplementation of the media. In the absence of serum, 45Ca release was significantly stimulated by 10(-7) M cortisol (treatment/control 1.37 +/- 0.06, P less than 0.005) and by 10(-6) M cortisol (treatment/control 1.27 +/- 0.08, P less than 0.005). The stimulation of resorption by 10(-7) M hydrocortisone was progressive from 24 to 96 hours of incubation. In contrast, when calvaria were incubated in the presence of 5% serum, bone resorption was not increased by cortisol (10(-8) M-10(-6) M). In the presence of 5% charcoal-stripped, heat-inactivated serum, there was a small stimulation of 45Ca release at 10(-6) M hydrocortisone only (treatment/control 1.19 +/- 0.06, P less than 0.01). Incubation of bones with indomethacin did not modify the effect of cortisol in either the presence or absence of serum. In serum-free conditions, cortisol 10(-8) M significantly inhibited the rate of thymidine incorporation, though at higher concentrations this effect was not seen. Cortisol produced a dose-related inhibition of serum-stimulated thymidine incorporation. It is concluded that the presence of serum substantially modifies the effect of cortisol on basal bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗