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Biomedical subjects

Ian R Reid

Publications and source records attributed to Ian R Reid.

At least 37 records · Page 2Linked to original sources
PubMed2005

Emerging and potential therapies for osteoporosis.

Osteoporotic fractures are an important public health problem, contributing substantially to morbidity and mortality in an ageing world population and consuming considerable health resources. Currently available pharmacological therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Considerable efforts are being made to develop new, more effective treatments for osteoporosis and to refine/optimise existing therapies. These novel treatments include an expanding array of drugs that primarily inhibit osteoclastic bone resorption; oestrogenic compounds, bisphosphonates, inhibitors of receptor activator of nuclear factor-kappaB ligand signalling, cathepsin K inhibitors, c-src kinase inhibitors, integrin inhibitors and chloride channel inhibitors. The advent of intermittent para-thyroid hormone (PTH) therapy has provided proof-of-principle that osteo-blast-targeted (anabolic) agents can effectively prevent osteoporotic fractures, and is likely to be followed by the introduction of other therapies based upon PTH, such as orally active PTH analogues, antagonists of the calcium sensing receptor, PTH-related peptide analogues, and/or agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling, sclerostin and matrix extracellular phosphoglycoprotein).

Anabolic Agents↗
PubMed2005

Lactoferrin--a novel bone growth factor.

Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. It is present in breast milk, in epithelial secretions, and in the secondary granules of neutrophils. In healthy subjects lactoferrin circulates at concentrations of 2-7 x 10(-6) g/ml. Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently, we have shown that lactoferrin can also promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through LRP1, a member of the family of low-density lipoprotein receptor-related proteins that are primarily known as endocytic receptors. Using confocal laser scanning microscopy, we demonstrated that fluorescently labeled lactoferrin is endocytosed and can be visualized in the cytoplasm of primary osteoblastic cells. Lactoferrin also induces activation of p42/44 MAPK signaling in primary osteoblasts, but the two pathways seem to operate independently as activation of MAPK signaling, but not endocytosis, is necessary for the mitogenic effect of lactoferrin. We conclude that lactoferrin may have a physiological role in bone growth and healing, and a potential therapeutic role as an anabolic factor in osteoporosis.

Animals↗
PubMed2005

Increased abdominal fat in young women of Indian origin.

People of Indian origin develop type 2 diabetes at a relatively young age and low body mass index compared to people of other racial groups, possibly because of preferential accumulation of abdominal fat. We examined the relationship between abdominal fat and body mass index (BMI) in healthy premenopausal women of different racial groups, and compared abdominal fat measurements at different ages. Women of Chinese, European, Indian or Polynesian origin (50 of each, mean age 31) had dual energy x-ray absorptiometry of the lumbar spine, with estimation of the percentage fat in the abdominal area. Polynesian women had a significantly greater mean BMI (P< 0.001) than all other groups, and a higher abdominal fat than European and Chinese woman (P< 0.001). Although the Indian women had a similar mean BMI to the European and Chinese women, they had a significantly greater abdominal fat (P<0.001). When examined by age tertile, the Indian women had significantly more abdominal fat than Chinese or European women at all ages (P<0.001), with marked differences evident even in the youngest group (mean age 23 years). Compared to other racial groups, women of Indian origin preferentially accumulate abdominal fat--a trait that is well established in young adulthood.

Abdomen↗
PubMed2004

Association between primary hyperparathyroidism and increased body weight: a meta-analysis.

Although primary hyperparathyroidism is frequently asymptomatic, it has been associated with an increased prevalence of hypertension, insulin resistance, dyslipidemia, cardiovascular mortality, and cancer. Previously we reported that patients with primary hyperparathyroidism are heavier than age-matched controls. Increased body weight could contribute to the association between primary hyperparathyroidism and these extraskeletal complications. We searched MEDLINE for English language studies published between 1975 and 2003 that reported body weight or body mass index in subjects with primary hyperparathyroidism and a healthy age- and sex-comparable eucalcemic control group. Seventeen eligible studies were identified. Subjects with primary hyperparathyroidism were 3.34 kg (95% confidence interval, 1.97-4.71; P < 0.00001) heavier than controls in 13 studies reporting body weight. In four studies reporting body mass index, subjects with primary hyperparathyroidism had an increased body mass index of 1.13 kg/m(2) (-0.29 to 2.55; P = 0.12) compared with controls. Standard mean difference analysis showed that subjects with primary hyperparathyroidism had an increased weight or body mass index of 0.3 sd (0.19-0.40; P < 0.00001) compared with controls. We conclude that patients with primary hyperparathyroidism are heavier than their eucalcemic peers, and that increased body weight may contribute to the reported associations between primary hyperparathyroidism and some extraskeletal complications.

Body Weight↗
PubMed2004

beta-Blocker use, BMD, and fractures in the study of osteoporotic fractures.

UNLABELLED: A role for osteoblastic beta-adrenoreceptors in bone regulation is suggested by the finding that beta-blockers increase bone mass in mice. We studied the association of beta-blocker use with BMD and fractures in the Study of Osteoporotic Fractures. beta-blocker use and BMD are unrelated in this cohort, and associations with fracture risk are inconsistent. INTRODUCTION: The central nervous system has been shown to regulate bone mass in mice, possibly by way of the beta(2)-adrenoreceptors on osteoblasts. beta-blockers have been shown to increase bone mass in mice. Because these agents are widely used therapeutically, it is possible that they may influence fracture epidemiology in humans, and they are a potential therapy for osteoporosis. MATERIALS AND METHODS: We have studied the association of beta-blocker use with BMD and fracture rates in the Study of Osteoporotic Fractures. beta-blocker use was recorded at the fourth visit, in 8412 women, of whom 1099 were users, and these women were followed for 7 years. RESULTS: Users had significantly higher weight, more thiazide use, more estrogen use, less glucocorticoid use, more statin use, and more hypertension than nonusers, and they smoked less. Total hip BMD at the fourth visit was higher in the beta-blocker users (0.746 versus 0.735 g/cm(2), p = 0.02), but adjustment for weight alone, or together with these other variables, eliminated this difference (p = 0.62). There was no effect of beta-blocker use on loss of hip BMD over a mean follow-up of 4 years (p = 0.48). Os calcis BMD at visit 4 was also higher in those taking beta-blockers (0.385 versus 0.375 g/cm(2), p = 0.005), but weight adjustment eliminated this difference (p = 0.14). The frequencies of hip or any fracture (since age 50) were similar in users and nonusers (p = 0.80 and p = 0.51, respectively). Over a mean follow-up of 7 years, there were 2167 total fractures, including 431 at the wrist and 585 at the hip. Among beta-blocker users, hazards ratios were 0.92 (0.81, 1.05) for any fracture, 0.74 (0.54, 1.01) for wrist fracture, and 0.76 (0.58, 0.99) for hip fracture. Adjustment for weight and other factors previously shown to influence hip fracture incidence in this cohort made little difference to the outcome. When fracture data were analyzed for nonselective and beta(1)-selective agents separately, trends toward fewer fractures were confined to the users of selective beta(1)-blockers. CONCLUSIONS: beta-Blocker use and BMD are unrelated in this cohort, and associations with fracture risk are inconsistent. Therefore, a history of use of these drugs is not useful in assessing fracture risk, nor do they have a role in osteoporosis management at this time. The relationship between beta-blocker use and hip fracture deserves further study.

Adrenergic beta-Antagonists↗
PubMed2004

Association of fat-free mass and training status with left ventricular size and mass in endurance-trained athletes.

OBJECTIVES: We sought to study the relationship between left ventricular (LV) size and body composition in male endurance athletes and age-matched control subjects. BACKGROUND: Endurance training is associated with increases in both left ventricular mass (LVM) and left ventricular end-diastolic dimension (LVEDD) in athletes. In other populations, LVM is independently predicted by fat-free mass (FFM). We hypothesized that the increase in LV size and mass observed with training may be a normal response to increased FFM. METHODS: Twelve young and 18 older male endurance athletes and 10 young and 18 older untrained men underwent exercise testing, echocardiography, and dual-photon x-ray absorptiometry body composition analysis. Univariate correlates (Spearman) and multivariate determinants of LVM and LVEDD were sought from: height, height(1.4), height(2.7), height(3.0), body surface area (BSA), FFM, weight, and body mass index. Un-indexed and indexed LVM and LVEDD were then compared. RESULTS: Athletes were of a similar age, weight, and height, but had higher FFM and maximum oxygen uptake than untrained men. Both LVM and LVEDD were correlated with body size, including FFM, BSA, weight, and height (all p < 0.05). On multivariate analysis, FFM was the only independent predictor of both LVM (R(2) = 0.36, p < 0.001) and LVEDD (R(2) = 0.35, p < 0.001). Furthermore, LVM and LVEDD (un-indexed and indexed to BSA and height) were different between athletes and non-athletes, but not when indexed to height(2.7) or FFM. CONCLUSIONS: Both LVM and LVEDD are predicted by FFM in endurance athletes, and when indexed to FFM, no training-related differences were observed. Thus, the extent of LV remodeling (athletic heart) in trained individuals may reflect a normal physiologic response to increased FFM induced by training.

Absorptiometry, Photon↗
PubMed2004

The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells.

Lactoferrin induces osteoblast proliferation and survival in vitro and is anabolic to bone in vivo. The molecular mechanisms by which lactoferrin exerts these biological actions are not known, but lactoferrin is known to bind to two members of the low-density lipoprotein receptor family, low- density lipoprotein receptor-related proteins 1 (LRP1) and 2 (LRP2). We have examined the role(s) of these receptors in the actions of lactoferrin on osteoblasts. We show that lactoferrin binds to cultured osteoblastic cells, and that LRP1 and LRP2 are expressed in several osteoblastic cell types. In primary rat osteoblastic cells, the LRP1/2 inhibitor receptor associated protein blocks endocytosis of lactoferrin and abrogates lactoferrin-induced p42/44 MAPK signaling and mitogenesis. Lactoferrin-induced mitogenesis is also inhibited by an antibody to LRP1. Lactoferrin also induces receptor associated protein-sensitive activation of p42/44 MAPK signaling and proliferation in osteoblastic human SaOS-2 cells, which express LRP1 but not LRP2. The mitogenic response of LRP1-null fibroblastic cells to lactoferrin is substantially reduced compared with that of cells expressing wild-type LRP1. The endocytic and signaling functions of LRP1 are independent of each other, because lactoferrin can activate mitogenic signaling in conditions in which endocytosis is inhibited. Taken together, these results 1) suggest that mitogenic signaling through LRP1 to p42/44 MAPKs contributes to the anabolic skeletal actions of lactoferrin; 2) demonstrate growth-promoting actions of a third LRP family member in osteoblasts; and 3) provide further evidence that LRP1 functions as a signaling receptor in addition to its recognized role in ligand endocytosis.

Animals↗
PubMed2004

Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo.

Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils. We found it to be present in fractions of milk protein that stimulated osteoblast growth, so we assessed its effects on bone cell function. Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1-100 microg/ml). Maximal stimulation was 5-fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50-70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes. Purified, recombinant, human, or bovine lactoferrins had similar potencies. In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 microg/ml, associated with decreased expression of receptor activator of nuclear factor-kappaB ligand. In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts. Lactoferrin was administered over calvariae of adult mice for 5 d. New bone formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth.

Animals↗
PubMed2004

Shared pathways of osteoblast mitogenesis induced by amylin, adrenomedullin, and IGF-1.

Amylin and adrenomedullin, members of the calcitonin peptide family, are anabolic to bone. Here, we report overlapping molecular mechanisms by which amylin, adrenomedullin, and IGF-1 induce osteoblast proliferation. Co-treatment of osteoblastic cells with amylin or adrenomedullin and IGF-1 failed to induce an additive mitogenic effect. In osteoblastic cells, neutralization of the IGF-1 receptor blocked the proliferative effects of amylin and adrenomedullin, while neutralization of IGF-1 did not. Neither amylin- nor adrenomedullin-induced mitogenic signaling or cell proliferation in IGF-1 receptor-null fibroblasts. In addition, amylin and adrenomedullin receptor blockers inhibited the proliferative effects of IGF-1 in osteoblastic cells. These findings demonstrate overlap in the molecular mechanisms by which amylin, adrenomedullin, and IGF-1 induce mitogenesis in osteoblasts, and an important role for the IGF-1 receptor in the mitogenic actions of amylin and adrenomedullin. Our findings are potentially important in refining these peptides for the therapy of osteoporosis.

Adrenomedullin↗
PubMed2004

A comparison of the effects of raloxifene and conjugated equine estrogen on bone and lipids in healthy postmenopausal women.

BACKGROUND: Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations, there are few direct comparative data. METHODS: Randomized placebo-controlled trial for 3 years, intention-to-treat analysis. Six hundred nineteen postmenopausal women with prior hysterectomy (mean age, 53.0 years) were studied in 38 centers in Europe, North America, Australasia, and South Africa. They were randomized to 60 mg/d or 150 mg/d of raloxifene, 0.625 mg/d of conjugated equine estrogen (CEE), or placebo. Bone density of the lumbar spine and proximal femur, biochemical markers of bone turnover, and fasting serum lipid concentrations were assessed for 3 years. RESULTS: Compared with baseline, bone density in the lumbar spine progressively declined by 2.0% in the placebo group (P <.05), was stable in the 2 raloxifene groups, and increased 4.6% in the subjects receiving CEE (P <.001). Effects in both raloxifene groups were different from those observed in the CEE and placebo groups (P <.001). Bone density in the total hip showed similar results. Conjugated equine estrogen produced significantly greater depression of serum osteocalcin, bone-specific alkaline phosphatase, and urine C-telopeptide, compared with raloxifene. Each of the active treatments caused comparable depression of low-density lipoprotein cholesterol below placebo levels (P <.001 at most time points). Raloxifene did not affect high-density lipoprotein cholesterol, whereas CEE increased it by 13.4% compared with placebo at 3 years (P <.001). Triglyceride concentrations increased 24.6% in the CEE group at 3 years (P <.003), a significantly greater change than in the raloxifene groups, which were 4.9% and 8.0% above baseline (P < or =.002) but not different from placebo. Urinary incontinence was reported in 11 women receiving CEE, but in only 1 or 2 in each of the other groups (P < or =.01 compared with the other groups). Hernias occurred less frequently in those receiving 150 mg/d of raloxifene or CEE (P =.03 vs placebo). CONCLUSIONS: Raloxifene and CEE have beneficial effects on bone density and bone turnover, although effects of CEE are more marked. Raloxifene and CEE produce different patterns of lipid responses and have distinct adverse effect profiles.

Alkaline Phosphatase↗
PubMed2004

Comparative responses of bone turnover markers to bisphosphonate therapy in Paget's disease of bone.

The measurement of biochemical markers of bone turnover is integral to the diagnosis and management of Paget's disease. Recently, there has been a proliferation of new markers and a move to carry out existing assays on automated platforms. We have assessed the performance of seven currently available markers in 20 patients with Paget's disease undergoing ibandronate therapy (6 or 12 mg) and in nine placebo-treated controls. Samples were collected at baseline and 6 months following intervention. The mean reductions in serum markers following treatment with either dose of ibandronate were: total alkaline phosphatase (AP; Roche Modular) 70%, bone AP (Beckman Access, Ostase) 80%, osteocalcin (Roche Elecsys 2010) 33%, beta-C-terminal telopeptide of type I collagen (betaCTX; Roche Elecsys 2010) 50%, and procollagen-N-terminal peptide (P1NP; Roche Elecsys 2010) 80%. For urine markers the reductions were: free deoxypyridinoline/creatinine (fDPD/creat) (DPC Immulite 2000) 36%, and N-telopeptide/creatinine (NTX/creat) (Osteomark) 81%. Total AP, bone AP, P1NP, and NTX all showed >95% of subjects to have abnormal values at baseline, reducing to 15-30% following treatment, and these treatment effects were highly significant (P < or = 0.0005), except for NTX (P = 0.02). The poorer precision of NTX reduced its utility. Baseline sensitivity was lower for the other markers (osteocalcin 68% of subjects abnormal, fDPD 22%, betaCTX 50%). Total AP, bone AP, and P1NP are suitable osteoblast markers for monitoring bisphosphonate therapy in Paget's disease, with performance approaching that of bone scintigraphy. NTX is less sensitive in detecting the effects of therapy, but is the best performing bone resorption marker. There is no clear evidence from this study that any of these newer markers are superior to total AP in assessing patients with this severity of Paget's disease.

Aged↗
PubMed2004

Effects of calcium supplementation on circulating lipids: potential pharmacoeconomic implications.

For about a century there has been recognition that calcium and lipids bind to one another in the gut, each interfering with the other's absorption. Calcium also causes malabsorption of bile acids, which is likely to contribute further to malabsorption of fat. High dietary calcium intakes may also have stimulatory effects on lipolysis. These mechanisms provide a basis for hypothesising that calcium supplementation may impact on circulating lipid concentrations, and there is now a significant amount of observational and trial data indicating that this is the case. The largest randomised controlled trial of calcium effects on lipids was carried out in 223 healthy postmenopausal women, and found that low density lipoprotein-cholesterol (LDL-C) decreased 6.3% and high density lipoprotein-cholesterol (HDL-C) increased by 7.3% at 1-year. The resultant 16.4% increase in HDL-C/LDL-C ratio would be predicted to reduce cardiovascular event rates by 20-30%, which is consistent with the available observational data. There are no trial data addressing this question and it is possible that other lipid-lowering agents, such as hydroxymethylglutaryl coenzyme A reductase inhibitors, might impact on cardiac event rates by mechanisms other than by lowering cholesterol levels. Therefore, caution is appropriate in incorporating these findings into clinical practice, but the balance of evidence suggests that calcium is a cost-effective adjunct to the dietary management of hyperlipidaemia.

Calcium↗
PubMed2003

Effect of sub-elite competitive running on bone density, body composition and sexual maturity of adolescent females.

The attainment of optimal peak bone mass during adolescence is important in the primary prevention of osteoporosis. Exercise may contribute to skeletal development and bone density during growth, although competitive exercise is suggested to have an adverse effect. This study assesses the effect of moderate exercise on the bone density of adolescent females. Additionally, other factors which significantly influence attainment of peak bone mass were identified. This was a cross-sectional study of 42 adolescent females, classified as runners (n=15) or non-runners (n=27). Nutrient intake, energy expenditure, menstrual history and pubertal stage were recorded. Bone age, skinfold thickness, body composition and bone mineral density (BMD) of total body, lumbar spine and proximal femur were measured. Statistical analyses used Student's t-test, Pearson correlation and multiple regression analyses. Runners had lower fat mass and higher lean mass, with a trend to higher BMD in all sites measured. There were no significant differences in menstrual cycle regularity, age at menarche or number who had attained menarche. Pubic hair development was similar in both groups. Breast development was delayed in runners, although this may have been a function of lower fat mass in this group. When subjects were categorized according to menarchal status, postmenarchal girls were significantly taller and heavier, with higher fat mass and significantly higher total body and lumbar spine BMD. There was no significant relationship between BMD at any site and dietary nutrient intake. Multiple regression analyses, using BMD as the dependent variable, identified running status, pubertal stage, fat mass and lean mass as significant determinants. When BMD/height was used, significant determinants in total body BMD were fat mass, pubertal stage and running status, while in the lumbar spine, only the latter two variables remained significant. In conclusion, body composition, physical activity and sexual maturity were identified as significant determinants of bone density during adolescence. Runners had significantly lower body fat than non-runners, but this did not interfere with hormonal cyclicity, and caused no detriment to their bone density. The results of this study are reassuring, since they indicate that sub-elite competitive athletics has no detrimental effect on bone mass accrual in adolescent females.

Adolescent↗
PubMed2003

alpha -melanocyte-stimulating hormone is a novel regulator of bone.

alpha-Melanocyte-stimulating hormone (alpha-MSH), a 13-amino acid peptide produced in the brain and pituitary gland, is a regulator of appetite and body weight, and its production is regulated by leptin, a factor that affects bone mass when administered centrally. alpha-MSH acts via melanocortin receptors. Humans deficient in melanocortin receptor 4 (MC4-R) have increased bone mass, and MC4-R has been identified in an osteoblast-like cell line. Thus alpha-MSH may act directly on the skeleton, a question addressed by the present studies. In primary cultures of osteoblasts and chondrocytes, alpha-MSH dose dependently (>or=10(-9) M) stimulated cell proliferation. In bone marrow cultures, alpha-MSH (>10(-9) M) stimulated osteoclastogenesis. Systemic administration of alpha-MSH to mice (20 injections of 4.5 microg/day) decreased the trabecular bone volume in the proximal tibiae from 19.5 +/- 1.8 to 15.2 +/- 1.4% (P = 0.03) and reduced trabecular number (P = 0.001). Radiographic indexes of trabecular bone, assessed by phase-contrast X-ray imaging, confirmed the bone loss. It is concluded that alpha-MSH acts directly on bone, increasing bone turnover, and, when administered systemically, it decreases bone volume. The latter result may also be contributed to by alpha-MSH effects elsewhere, such as the adipocyte, pancreatic beta-cell, or central nervous system.

Animals↗
PubMed2003

Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review.

OBJECTIVES: identify, appraise, and synthesize data from randomized, controlled trials of vitamin D supplementation in older people. DESIGN: A systematic review of trials identified from searches of databases, reference lists, review articles, and recent conference proceedings. SETTING: Most studies performed in ambulatory setting. PARTICIPANTS: Older people (mean age=60). INTERVENTIONS: Vitamin D or vitamin D metabolites. MEASUREMENTS: Strength, physical performance, or falls. RESULTS: Thirteen trials involving 2,496 patients met this study's inclusion criteria. Most of the trials were small and had methodological problems. In 10 trials, there was no evidence that vitamin D or vitamin D metabolites had an effect on falls or physical function, but three trials showed a positive effect of vitamin D in combination with calcium. When available data from the four highest quality trials were pooled (n=1,317), there continued to be no evidence that vitamin D reduced the risk of falling (relative risk= 0.99, 95% confidence interval=0.89-1.11), although a single trial of vitamin D and calcium showed a positive effect. CONCLUSION: Although there is insufficient evidence that vitamin D supplementation alone improves physical performance in older people, some data suggest a benefit from vitamin D combined with calcium supplementation, but this requires confirmation in large, well-designed trials.

Accidental Falls↗
PubMed2003

Bisphosphonates: new indications and methods of administration.

In the course of 2002, several new studies were published confirming the efficacy of bisphosphonate drugs in fracture prevention in patients with osteoporosis. Further evidence was provided of their long duration of action, making intermittent administration possible. The potent bisphosphonate zoledronate can be given at intervals of as long as 1 year and produces changes in bone density and in markers of bone turnover comparable with those seen with conventional daily oral dosing with alendronate or risedronate. If such regimens are proven to prevent fractures, their convenience is likely to result in their widespread adoption and potentially an increase in compliance with these medications. Further evidence has been presented documenting the value of bisphosphonates in preventing the skeletal complications of malignancy, and possibly in reducing mortality in patients with breast cancer. The role of bisphosphonates in osteogenesis imperfecta was further confirmed, and novel roles in ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy were suggested.

Alendronate↗
PubMed2003

Calcium sensing receptor gene A986S polymorphism and responsiveness to calcium supplementation in postmenopausal women.

Recently several studies in adolescent girls or premenopausal women have implicated the calcium sensing receptor (CASR) gene A986S polymorphism in calcium and bone metabolism. However, the role of this genetic variant in postmenopausal women, specifically the development of osteoporosis, is unknown. This study reports the findings of a randomized, double-blind, placebo-controlled study of healthy postmenopausal women followed for 2 yr while taking placebo or supplementary calcium. Specifically, we examined the relationship between the CASR A986S polymorphism, bone biochemical profile, and bone mineral density at baseline and after 2 yr of treatment. We found no effect of this genetic variant in postmenopausal women at baseline or in response to calcium supplementation. These results are in contrast to those in young or premenopausal women, and they provide no support for an important role for the CASR A986S polymorphism in osteoporosis.

Bone Density↗