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Biomedical subjects

Ian R Reid

Publications and source records attributed to Ian R Reid.

At least 19 recordsLinked to original sources
PubMed2007

Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial.

CONTEXT: Recent studies have reported low bone mineral density (BMD) in HIV-infected patients. Annual iv administration of 4 mg zoledronate has been shown to increase BMD and suppress bone turnover in postmenopausal women. OBJECTIVE: The objective of the study was to determine whether annual administration of 4 mg zoledronate will increase BMD in HIV-infected men receiving highly active antiretroviral therapy. DESIGN AND SETTING: A 2-yr randomized placebo-controlled trial was conducted in a clinical research center. PARTICIPANTS: A total of 43 HIV-infected men were treated with highly active antiretroviral therapy for at least 3 months, with BMD T score less than -0.5. INTERVENTION: Participants received annual iv administration of 4 mg zoledronate or placebo. All participants took 400 mg/d calcium and 1.25 mg/month vitamin D. MEASUREMENTS: BMD at the lumbar spine, total hip and total body, and bone turnover markers were measured. RESULTS: At the lumbar spine, BMD increased by 8.9% over 2 yr in the zoledronate group compared with an increase of 2.6% in the control group (P<0.001). At the total hip, BMD increased by 3.8% over 2 yr in the zoledronate group compared with a decrease of 0.8% in the control group (P<0.001). At the total body, BMD increased by 2.3% over 2 yr compared with a decrease of 0.5% in the control group (P<0.001). Urine N-telopeptide decreased by 60% at 3 months in the zoledronate group and thereafter remained stable. CONCLUSIONS: Annual administration of zoledronate is a potent and effective therapy for the prevention or treatment of bone loss in HIV-infected men. The current data provide the first trial evidence of the BMD effects of annual zoledronate beyond 1 yr in any population, as well as being the first reported trial in men.

Adult↗
PubMed2007

Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate.

UNLABELLED: A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy. INTRODUCTION: Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease. MATERIALS AND METHODS: This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n = 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion. RESULTS: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers. CONCLUSIONS: ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.

Administration, Oral↗
PubMed2007

Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone.

UNLABELLED: Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.

Aged↗
PubMed2006

Randomized controlled trial of calcium in healthy older women.

PURPOSE: Calcium has been shown to have positive effects on bone mineral density in postmenopausal women. However, these effects are small, it is unknown whether they are sustained with long-term use, they have not been shown with intention-to-treat analyses, and the evidence for fracture prevention with calcium monotherapy is inconsistent. METHODS: A randomized controlled trial of calcium (1 g/day as the citrate) in 1471 healthy postmenopausal women (aged 74+/-4 years) was performed to assess the effects on bone density and fracture incidence over 5 years. RESULTS: Follow-up was complete in 90% of subjects, and average medication compliance was 55% to 58%. Calcium had a significant beneficial effect on bone density (intention-to-treat analysis), with between-groups differences at 5 years of 1.8% (spine), 1.6% (total hip), and 1.2% (total body). Effects were greater in a per-protocol analysis (5-year differences of 2.3%, 2.8%, and 1.8%, respectively). A total of 425 fractures occurred in 281 women. Hazard ratios, based on time to first fracture, were 0.90 (95% confidence interval [CI], 0.71-1.16) for any symptomatic fracture, 0.72 (95% CI, 0.44-1.18) for vertebral, 3.55 (95% CI, 1.31-9.63) for hip, and 0.65 (95% CI, 0.41-1.04) for forearm fracture. Per-protocol analysis found respective hazard ratios of 0.86 (95% CI, 0.64-1.17), 0.62 (95% CI, 0.33-1.16), 3.24 (95% CI, 0.65-16.1), and 0.45 (95% CI, 0.24-0.87). Height loss was reduced by calcium in the per-protocol population (P=.03). Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years, but constipation was more common. CONCLUSIONS: Calcium results in a sustained reduction in bone loss and turnover, but its effect on fracture remains uncertain. Poor long-term compliance limits its effectiveness.

Aged↗
PubMed2006

Bone mineral density is not reduced in HIV-infected Caucasian men treated with highly active antiretroviral therapy.

OBJECTIVE: Recent studies have reported low bone mineral density (BMD) in patients infected with human immunodeficiency virus (HIV). Frequently these findings have been attributed to treatment with highly active antiretroviral therapy (HAART). We sought to determine whether BMD in HIV-infected men treated with HAART for at least 3 months is different from that in healthy controls, and, if so, what HIV-related factors might explain this finding. DESIGN: Cross-sectional analysis. PATIENTS: Fifty-nine HIV-infected Caucasian men treated with HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age-matched (within 5 years) to two controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters. RESULTS: The mean duration of known HIV infection was 8.5 years, and of treatment with HAART was 52 months. There was no significant difference in mean BMD between groups at the lumbar spine (HIV group: 1.23 g/cm2, controls: 1.25 g/cm2; P = 0.53) or total body (HIV group: 1.18 g/cm2, controls: 1.20 g/cm2; P = 0.09). At the total hip the HIV-infected group had significantly lower BMD than the control group (HIV group: 1.03 g/cm2, controls: 1.09 g/cm2; P = 0.01). The HIV-infected group were, on average, 6.3 kg lighter than the controls. After adjusting for this weight difference, HIV infection was not an independent predictor of BMD at any site (lumbar spine P = 0.79; total hip P = 0.18; total body P = 0.76). CONCLUSIONS: HIV-infected men treated with HAART are lighter than healthy controls. This weight difference is responsible for a small decrement in hip BMD. Overall, BMD is not significantly reduced in HIV-infected Caucasian men treated with HAART.

Analysis of Variance↗
PubMed2005

Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women.

Previously, we reported that people with elevated parathyroid hormone (PTH) levels due to primary hyperparathyroidism have increased body weight compared to eucalcemic controls. We sought to determine whether the same relationship between PTH and body weight exists in eucalcemic healthy postmenopausal women, and to investigate the relationships between components of body weight, PTH, vitamin D metabolites, and metabolic indices. We performed a cross-sectional analysis of 116 healthy community-dwelling postmenopausal women. Pearson correlation analysis was used to test for univariate linear relationships between variables, and stepwise multiple regression analysis to assess for multivariate relationships. We found that PTH was significantly positively correlated with body weight, regional and total fat mass, and percent body fat, and negatively correlated with activity levels, 25 hydroxyvitamin D (25OHD), dietary calcium intake, and serum phosphate. On multivariate analysis, PTH was positively related to percent body fat (P = 0.020; partial r2 = 0.10) and negatively related to dietary calcium intake (P = 0.041; partial r2 = 0.03) and serum phosphate (P = 0.026; partial r2 = 0.04). Adjusting for vitamin D insufficiency or 25OHD levels did not affect the relationship between PTH and fat mass. For 25OHD, there were significant positive correlations with lumbar spine BMD and serum albumin, and significant negative correlations with PTH, total fat mass, trunk fat, and pelvic fat. On multivariate analysis, 25OHD was positively related to serum albumin (P = 0.008; partial r2 = 0.07) and negatively related to pelvic fat mass (P = 0.014; partial r2 = 0.05). Adjusting for PTH levels did not change the relationship between 25OHD and pelvic fat mass. We conclude that fat mass is a significant independent determinant of serum PTH levels, and that this relationship is independent of the inverse relationship between 25OHD and fat mass. This association between fat mass and PTH might contribute to the association between primary hyperparathyroidism and increased body weight.

Adipose Tissue↗
PubMed2005

Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease.

BACKGROUND: The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs. METHODS: In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled. RESULTS: At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P<0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P<0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers. The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months. Pain scores improved in both groups. During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P<0.001). CONCLUSIONS: A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.

Administration, Oral↗
PubMed2005

Determinants of vitamin D status in older women living in a subtropical climate.

Studies performed in the Northern Hemisphere and in areas distant from the equator have demonstrated significant seasonal variation in 25-hydroxyvitamin D (25OHD) levels. Whether such variation occurs in a subtropical area such as Australasia is not clear. We performed a cross-sectional study of 1,606 healthy, postmenopausal women recruited over a 33-month period. The study had three goals: to determine the normal levels of 25OHD in healthy postmenopausal women living in Auckland, New Zealand; to determine whether seasonal variation of 25OHD occurs at this latitude; to assess the relationship between 25OHD, biochemical indices, anthropometric variables and bone mineral density (BMD). We found significant seasonal variation in 25OHD levels, with the change in monthly ultraviolet dose from summer to winter being followed 6-8 weeks later by a corresponding change in 25OHD levels. Vitamin D insufficiency (25OHD <50 nmol/l) was common. During summer, 28-58% of participants had suboptimal vitamin D status, while in winter, the frequency increased to 56-74%. 25OHD levels correlated with participants' age (r=-0.15), weight (r=-0.11), body mass index (r=-0.13), fat mass (r=-0.14), percentage body fat (r=-0.16), physical activity (r=0.10) and the month of blood sampling (all P<0.0001). Collectively, age, fat mass, physical activity, and month of sampling explained 21% of the variance in 25OHD. No significant relationships were noted between 25OHD and BMD at any site. Other variables that showed significant monthly variation were glucose (P=0.002), serum phosphate, alkaline phosphatase, and albumin (all P<0.0001). There was no monthly variation in BMD at the lumbar spine or proximal femur. In conclusion, there is significant seasonal variation in 25OHD levels, even in a subtropical climate. Furthermore, despite generous amounts of sunlight, considerable numbers of women have suboptimal vitamin D status, even in summer. Our findings support the suggestion that vitamin D supplementation should become standard practice in this population of women, particularly during winter.

Adipose Tissue↗
PubMed2005

Effects of a beta-blocker on bone turnover in normal postmenopausal women: a randomized controlled trial.

INTRODUCTION: The central nervous system has been demonstrated to regulate bone mass in mice, possibly via the beta2-adrenoreceptors on osteoblasts. beta-blockers increase bone mass in mice, and some observational studies have suggested a beneficial effect of these drugs on bone in humans EXPERIMENTAL SUBJECTS: We studied 41 normal postmenopausal women. MATERIALS AND METHODS: We conducted a randomized, placebo- controlled trial, comparing the effects on bone markers of propranolol 160 mg/d and placebo over 3 months. RESULTS: Serum osteocalcin declined by almost 20% in the first 2 wk of propranolol treatment, and this effect increased over time (P < 0.0001). Other osteoblast markers, procollagen type-I N-terminal propeptide and total alkaline phosphatase activity, were not significantly changed by propranolol. Urine free deoxypyridinoline declined by approximately 10% between 0 and 6 wk (P = 0.019) in the beta-blocker group and was stable thereafter. Serum C-terminal telopeptide of type I collagen also showed a small decrease, but this was not significantly different between groups. Serum albumin concentrations decreased by more than 2 g/liter in the first 2 wk of propranolol treatment, remaining stable subsequently (P = 0.007). Serum creatinine tended to increase in the propranolol group (P = 0.06), as did weight. Bone densities in the lumbar spine and total proximal femur did not change significantly in either group. CONCLUSIONS: The present study provides no evidence that beta-blocker drugs stimulate bone formation; if anything, propranolol reduces osteoblast activity. It also influences renal function and fluid balance, effects that might indirectly affect bone metabolism. Current evidence does not justify the use of beta-blockers for treatment of osteoporosis.

Adrenergic beta-Antagonists↗
PubMed2005

Effects of calcium supplementation on body weight and blood pressure in normal older women: a randomized controlled trial.

CONTEXT: Epidemiological data suggest that high calcium intakes are associated with decreased body weight and blood pressure. However, there is little evidence from randomized trials that addresses these important issues. OBJECTIVE: The objective of this study was to assess the long-term effects of calcium on body weight and blood pressure. DESIGN: This is a substudy of an ongoing, double-blind, randomized, controlled trial of calcium supplementation. End points were assessed at 30 months. SETTING: This study was performed at a university medical center. PARTICIPANTS: Normal postmenopausal women (mean age, 74 yr; mean weight, 67 kg; mean blood pressure, 134/70 mm Hg at baseline) participated in this study. INTERVENTION: Study subjects were treated with calcium (1 g/d; n = 732) and placebo (n = 739). MAIN OUTCOME MEASURES: Body weight and blood pressure were the main outcome measures. RESULTS: Weight decreased by 368 +/- 132 g (mean +/- se) with calcium treatment and by 369 +/- 134 g with placebo (P = 0.93). Fat and lean masses did not show an effect of calcium. Blood pressure showed transient reductions of 1-2 mm Hg at 6 months in the calcium group, resulting in a significant between-group difference only for systolic pressure (P = 0.048). At 30 months, the change from baseline in systolic pressure was 0.0 +/- 0.9 mm Hg in the calcium group and 2.4 +/- 0.9 mm Hg in the placebo group (P = 0.14). For diastolic pressures, the changes were -0.2 +/- 0.4 and 0.8 +/- 0.4 mm Hg, respectively (P = 0.13). In those with baseline calcium intakes less than 600 mg/d, the treatment effect was greater and did persist. CONCLUSIONS: Calcium supplementation of 1 g/d does not produce biologically significant effects on body weight, and its hypotensive effect is small and transient in most women.

Aged↗
PubMed2005

Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency.

Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium <12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] <20 microg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 microg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P < 0.01) and 26% at 12 months (P < 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = -0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.

Adult↗
PubMed2005

Comparison of the effects of pravastatin and atorvastatin on fracture incidence in the PROVE IT-TIMI 22 trial--secondary analysis of a randomized controlled trial.

Recent observational studies suggest that patients using statins have higher bone densities and lower fracture rates. However, this finding has not been supported by a secondary analysis of a large randomized controlled trial, assessing pravastatin. It has been suggested that the latter finding might be attributable to the failure of pravastatin, which is hydrophilic, to gain access to bone. The recently published TIMI 22 study, which compared pravastatin with more intensive therapy with the bone-active statin, atorvastatin, offers the possibility of re-assessing the effects of these agents, on fractures. This study assessed 4162 patients over a mean period of 24 months, and compared 40 mg of pravastatin daily with 80 mg of atorvastatin daily. There were 30 fractures in the pravastatin group and 31 in the atorvastatin group, producing a relative risk for any fracture of 1.02 (95% CI, 0.62-1.68) in the atorvastatin group. This study has sufficient fractures for a relative risk of fracture of 0.52 to be significant, which is of the order that has been observed in some of the observational studies. These data do not provide any support for the hypothesis that pravastatin and atorvastatin have different effects on fracture, and are consistent with the conclusions from the other controlled trials-that currently available statins do not impact on fracture risk.

Atorvastatin↗
PubMed2005

Comparison of dual-energy X-ray absorptiometry and conventional radiography for the detection of vertebral fractures.

Prevalent vertebral fractures confer a high risk of subsequent fractures; therefore, fracture identification is a key issue in osteoporosis management. Dual-energy X-ray absorptiometry has become the most widespread technique for the assessment of bone density, and can also provide images for assessment of vertebral morphometry (MXA) that are undistorted by parallax. The radiation dose is very low compared with conventional radiography. Whether the resolution of MXA is adequate for vertebral morphometry is uncertain. The present study compares MXA with conventional radiography in detecting vertebral deformities. MXA scans and lateral radiographs were performed in 61 women with osteoporosis. Adequate images were obtained in 99.1% of the 793 vertebrae by radiography and 95.6% by MXA. Poor image quality was mostly at T4-6 by MXA. Precision of repeat analyses was comparable between the techniques. Heights measured by MXA were 24 to 35% less than the radiographic values, the methods produced equivalent results for the ratio of anterior to posterior heights, but the MXA values for middle to posterior ratios were about 10% lower than for the radiographs (p < 0.0001). The extent of agreement between the techniques in identifying vertebral fractures was dependent on the strictness of the fracture definition used. With a 3 standard deviation (SD) criterion, the techniques found similar numbers of patients to have vertebral deformities, and the concordance in classification of individual vertebrae was 94%. At a 2 SD, cut-off concordance was 79%, and at 4 SD, it was 96%. Receiver-operating characteristic curves using cut-offs of > or = 3 SDs also showed excellent diagnostic accuracy. We conclude that MXA shows acceptable performance for clinical use in diagnosing vertebral deformities, as long as cut-offs of > or = 3 SDs are used, although a few percent of vertebrae in the upper thoracic region cannot be imaged adequately using this technique.

Absorptiometry, Photon↗