PubMed Health⌕ Search

Biomedical subjects

Ian R Reid

Publications and source records attributed to Ian R Reid.

46 records · Page 3Linked to original sources
PubMed2003

A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate.

Long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera) is associated with a reduction in bone mineral density (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss is not known, but the relative estrogen deficiency induced by DMPA use could be responsible. We have undertaken a randomized, double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score < or = 0). Nineteen women were allocated to receive conjugated estrogens (0.625 mg/d orally) and 19 to receive a matching placebo. All continued with regular DMPA injections throughout the study. Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body sites every 6 months for 2 yr; the main outcome measure being the change in areal BMD at the lumbar spine. At baseline, the two groups were well matched for demographic, anthropometric, and biochemical variables, and for BMD. Twenty-seven subjects completed at least 18 months in the study, and 26 the full 2 yr, with similar numbers dropping out from each group (mainly for personal reasons). In the estrogen-treated group, mean lumbar spine BMD increased 1%, whereas in the placebo group it fell 2.6%, over 2 yr. The between group differences were 2.0% at 12 months (P = 0.058), 3.2% at 18 months (P < 0.01), and 3.5% at 24 months (P < 0.002). Differences of lesser statistical magnitude were seen at the femoral neck (between group differences at 2 yr: 2.7%, P = 0.24), Ward's triangle (5.0%, P = 0.055), greater trochanter (3.6%, P = 0.056), total body (1.3%, P = 0.046), legs (1.3%, P = 0.065), and trunk (2.0%, P = 0.029). There were no major adverse events. These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy.

Absorptiometry, Photon↗
PubMed2002

A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype.

Idiopathic hyperphosphatasia is an autosomal recessive bone disease characterized by deformities of long bones, kyphosis and acetabular protrusion, increasing in severity as affected children pass through adolescence. Biochemical and histological evidence indicate that there is extremely rapid bone turnover, with indices of both bone resorption and formation greatly increased. A genome-wide search, in a family with three children affected by idiopathic hyperphosphatasia, suggested linkage to a locus on the long arm of chromosome 8 (8q24). The gene TNFRSF11B encoding osteoprotegerin (OPG), which lies within this locus, was an obvious candidate, given the critical role of OPG in regulating osteoclast development. All three affected siblings were homozygous for a 3 bp inframe deletion in exon 3 of the TNFRSF11B gene, resulting in the loss of an aspartate residue. Their parents (who were first cousins) were heterozygous for the mutation. Recombinant wild-type and mutant OPG cDNAs were expressed in human epithelial kidney cells, and secreted OPG was collected from the conditioned medium. In vitro measurements of bone resorption showed that wild-type OPG suppressed bone resorption, whereas the mutant form did not, confirming this to be an inactivating mutation. This description of abnormal OPG function in humans expands the spectrum of genetic bone diseases arising from perturbations of the OPG/RANK-L/RANK system that regulates osteoclastogenesis.

Adolescent↗
PubMed2002

Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial.

PURPOSE: To determine the effect of supplementation with calcium citrate on circulating lipid concentrations in normal older women. SUBJECTS AND METHODS: As part of a study of the effects of calcium supplementation on fractures, we randomly assigned 223 postmenopausal women (mean [+/- SD] age, 72 +/- 4 years), who were not receiving therapy for hyperlipidemia or osteoporosis, to receive calcium (1 g/d, n = 111) or placebo (n = 112) for 1 year. Fasting serum lipid concentrations, including high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, were obtained at baseline, and at 2, 6, and 12 months. RESULTS: After 12 months, HDL cholesterol levels and the HDL cholesterol to LDL cholesterol ratio had increased more in the calcium group than in the placebo group (mean between-group differences in change from baseline: for HDL cholesterol, 0.09 mmol/L (95% confidence interval [CI]: 0.02 to 0.17; P = 0.01); for HDL/LDL cholesterol ratio, 0.05 (95% CI: 0.02 to 0.08; P = 0.001). This was largely due to a 7% increase in HDL cholesterol levels in the calcium group, with a nonsignificant 6% decline in LDL cholesterol levels. There was no significant treatment effect on triglyceride level (P = 0.48). CONCLUSION: Calcium citrate supplementation causes beneficial changes in circulating lipids in postmenopausal women. This suggests that a reappraisal of the indications for calcium supplementation is necessary, and that its cost effectiveness may have been underestimated.

Aged↗
PubMed2002

Intravenous zoledronic acid in postmenopausal women with low bone mineral density.

BACKGROUND: Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored. METHODS: We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point. RESULTS: There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group. CONCLUSIONS: Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.

Aged↗
PubMed2002

Fractures between the ages of 20 and 50 years increase women's risk of subsequent fractures.

BACKGROUND: Perimenopausal and postmenopausal fractures are well-recognized, strong, independent predictors of subsequent fractures. However, it is unknown whether premenopausal fractures are predictive of postmenopausal fractures. OBJECTIVE: To determine whether self-reported fractures sustained before the age of 50 years are associated with fractures after this age. SUBJECTS AND METHODS: Cross-sectional study of 1284 women (mean +/- SD age, 73 +/- 4 years) who were 10 or more years' postmenopausal and who were recruited from electoral rolls in Auckland, New Zealand. Detailed information on their fracture, medical, menstrual, alcohol, and smoking histories was obtained using a standardized questionnaire. RESULTS: Nine percent of the women reported fractures before the age of 20 years; 7%, between the ages of 20 and 50 years; and 29%,after the age of 50 years. Fractures sustained between the ages of 20 and 50 years were associated with a 74% increase in the risk of fractures after the age of 50 years (odds ratio, 1.74; 95% confidence interval, 1.12-2.70), while fractures occurring before the age of 20 years were not (odds ratio, 1.01; confidence interval, 0.66-1.56). Multivariate analysis showed that after bone density, age, maternal history of hip fractures, age at menopause, weight, history of hormone replacement therapy, and smoking and alcohol histories were adjusted for, a history of fractures between the ages of 20 and 50 years remained a significant independent predictor of risk of fractures after the age of 50 years (risk ratio, 1.83; confidence interval, 1.12-2.76). CONCLUSIONS: Any fracture (unrelated to motor vehicle accidents) sustained between the ages of 20 and 50 years is associated with increased risk of fractures after the age of 50 years. Therefore, this is an important clinical risk factor that points to the need for bone density measurement, consideration of lifestyle modification, and antiosteoporosis therapies in these women.

Age Factors↗
PubMed2002

Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy.

OBJECTIVE: To prospectively assess bone density and the factors determining the rate of bone loss over a 10-year period of postmenopausal life. DESIGN: Prospective, observational study. METHODS: One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47-71 years) completed the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual-energy X-ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed. RESULTS: Twenty-four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow-up. The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT was associated with significant gains in bone density (total body + 3.0%, trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non-HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow-up bone densities in the non-HRT users were highly correlated (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted for the majority of the variance in the 10-year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow-up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health). CONCLUSIONS: Bone density is highly predictable over an extended period of time in normal postmenopausal women. Maintenance of body weight and good health reduce bone loss. HRT is effective for treating osteoporosis, with improvement in bone density and reduction in vertebral fractures. Good compliance with HRT long-term is achievable. These findings are relevant to deciding the frequency of bone density measurement, and in advising women regarding prevention and treatment of postmenopausal bone loss.

Aged↗
PubMed2002

Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception.

OBJECTIVE: The purpose of this study was to determine the rate of early postmenopausal bone loss in women who had used depot medroxyprogesterone acetate contraception through to menopause. STUDY DESIGN: Bone mineral density at the lumbar spine and femoral neck was assessed prospectively over 3 years in 15 women who reached a natural menopause and who did not undergo hormone replacement therapy and in 16 long-term users of depot medroxyprogesterone acetate who discontinued depot medroxyprogesterone acetate only on reaching menopause. Of the latter, 5 women subsequently underwent hormone replacement therapy. RESULTS: Early menopausal bone loss was rapid in the control group (6% from both sites over 3 years), but the users of depot medroxyprogesterone acetate (who did not take hormone replacement therapy) showed little change in bone mineral density. Between-group differences were statistically significant at years 2 and 3 at both sites (P <.03-<.002). In the users of depot medroxyprogesterone acetate who underwent hormone replacement therapy, bone mineral density increased significantly (P <.03) at the lumbar spine and was stable at the femoral neck. CONCLUSION: Women who use depot medroxyprogesterone acetate through to menopause have attenuated rates of bone loss from the lumbar spine and femoral neck, presumably because they have already lost the estrogen-sensitive component of bone.

Bone Density↗
PubMed2002

The phospholipids sphingosine-1-phosphate and lysophosphatidic acid prevent apoptosis in osteoblastic cells via a signaling pathway involving G(i) proteins and phosphatidylinositol-3 kinase.

The naturally occurring phospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have recently emerged as bioactive compounds that exert mitogenic effects in many cell types, including osteoblasts. In the current study, we examined the ability of each of these compounds to influence osteoblast survival. Using terminal deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling and DNA fragmentation assays, we found that both LPA and S1P dose-dependently inhibited (by at least 50% and 40%, respectively) the apoptosis induced by serum withdrawal in cultures of primary calvarial rat osteoblasts and SaOS-2 cells. The antiapoptotic effects were inhibited by pertussis toxin, wortmannin, and LY294002, implicating G(i) proteins and phosphatidylinositol-3 kinase (PI-3 kinase) in the signaling pathway that mediates phospholipid-induced osteoblast survival. Specific inhibitors of p42/44 MAPK signaling did not block LPA- or S1P-induced osteoblast survival. LPA and S1P induced PI-3 kinase-dependent activation of p70 S6 kinase, but rapamycin, a specific inhibitor of p70 S6 kinase activation, did not prevent phospholipid-induced osteoblast survival. LPA and S1P also inhibited apoptosis in Swiss 3T3 fibroblastic cells in a G(i) protein-dependent fashion. In fibroblastic cells, however, the antiapoptotic effects of S1P were sensitive to inhibition of both PI-3 kinase and p42/44 MAPK signaling, whereas those of LPA were partially abrogated by inhibitors of p42/44 MAPK signaling but not by PI-3 kinase inhibitors. These data demonstrate that LPA and S1P potently promote osteoblast survival in vitro, and that cell-type specificity exists in the antiapoptotic signaling pathways activated by phospholipids.

Animals↗
PubMed2002

Pharmacotherapy of osteoporosis in postmenopausal women: focus on safety.

The therapy of osteoporosis has made enormous strides in the last decade. There is now a range of interventions, each with its pros and cons. Calcium and vitamin D supplementation remain the foundation and have few safety issues. Bisphosphonates are widely used, though gastrointestinal tolerance is a problem with some oral preparations. Intravenous administration may circumvent this, although this introduces the smaller problem of acute phase reactions. The side effect profile of hormone replacement therapy (HRT) is still being delineated after 40 years of use, with substantial new information expected in the next few years. This will clarify its place in the medical management of the menopause. Raloxifene appears to have a superior safety profile to HRT, though its efficacy on bone may be less. While none of these options is suitable for everyone, the range of available therapies does mean that most patients can find an intervention that is effective and acceptable.

Calcitonin↗