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Biomedical subjects

Mark J Bolland

Publications and source records attributed to Mark J Bolland.

12 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

Delayed development of Paget's disease in offspring inheriting SQSTM1 mutations.

UNLABELLED: Familial Paget's disease is associated with mutations in SQSTM1. We compared the age at diagnosis and severity of Paget's disease in parents with SQSTM1 mutations to their offspring who inherited a mutation. At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents. INTRODUCTION: Mutations in sequestosome 1 (SQSTM1) occur in 25-50% of cases of familial Paget's disease and are thought to be disease-causing. We sought to determine whether there are differences in age at diagnosis and severity of disease in parents and their offspring who share the same genetic predisposition to Paget's disease. MATERIALS AND METHODS: Eighty-four offspring from 10 families (29 index patients with Paget's disease) with mutations in SQSTM1 were approached, and 58 agreed to participate. The ubiquitin-binding domain region of SQSTM1 was sequenced, and the presence or absence of the known mutation was established. The presence of Paget's disease in offspring who had inherited an SQSTM1 mutation was determined by bone scintigraphy and measurement of serum alkaline phosphatase (ALP). RESULTS: Twenty-three of 58 offspring had inherited a germline mutation in SQSTM1. The mean ALP was 77 U/liter in offspring with mutations and 72 U/liter in those without mutations (p=0.84). Scintiscans from four offspring (mean age, 45 years; mean ALP, 139 U/liter; mean skeletal involvement, 6%) showed evidence of Paget's disease but were normal in the other 19 (mean age, 44 years; mean ALP, 64 U/liter). In comparison, in the 15 parents of the 23 offspring, the mean age of diagnosis was 48 years, the mean ALP was 850 U/liter, and the mean skeletal involvement was 30%. There was a 63% reduction in the risk of being diagnosed with Paget's disease at a comparable age in the offspring compared with the parents (p=0.028). CONCLUSIONS: Only 17% of offspring inheriting an SQSTM1 mutation had evidence of Paget's disease on scintigraphy, and this was diagnosed at a later age and was less extensive than in their affected parents. SQSTM1 thus shows incomplete penetrance. The data are consistent with the hypothesis that an environmental factor is important in the pathogenesis and clinical phenotype of familial Paget's disease and that exposure to this factor may be falling.

Adaptor Proteins, Signal Transducing↗
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↗
PubMed2006

A case of low cortisol-binding globulin: use of plasma free cortisol in interpretation of hypothalamic-pituitary-adrenal axis tests.

We investigated a patient with suspected hypopituitarism who showed subnormal cortisol responses to stimulation tests with adrenocorticotrophic hormone (ACTH) and hypoglycaemia, but normal ACTH and 11-deoxycortisol responses in the metyrapone test. Cortisol-binding globulin (CBG) was measured by enzyme-linked immunosorbent assay (ELISA), and was used to calculate plasma free cortisol and free cortisol index. The patient had a low plasma CBG concentration. Reinterpreted in terms of free cortisol and free cortisol index, his responses to ACTH were normal. We conclude that despite subnormal total cortisol responses to ACTH and hypoglycaemia, the patient had a normal hypothalamic-pituitary-adrenal (HPA) axis. Measurement of CBG concentration and calculation of free cortisol or free cortisol index can help avoid false interpretations of dynamic tests of the HPA axis based on plasma total cortisol.

Adrenocorticotropic Hormone↗
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

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↗
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

Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole.

OBJECTIVE: To report a case of an interaction between inhaled corticosteroids and itraconazole causing iatrogenic Cushing's syndrome and provide a review of the relevant literature. CASE SUMMARY: A 70-year-old white woman on long-term treatment with high-dose inhaled corticosteroids for asthma was diagnosed as having Scedosporium apiospermum infection of the skin and subcutaneous tissues. As a result, she was treated with itraconazole for 2 months. She subsequently developed Cushing's syndrome due to a probable cytochrome P450-mediated interaction between itraconazole and budesonide. She also had secondary adrenal insufficiency requiring prolonged treatment with replacement hydrocortisone. DISCUSSION: Budesonide is a potent glucocorticoid that is metabolized in the liver by the CYP3A4 isoenzyme to inactive metabolites. Itraconazole is a potent cytochrome P450 inhibitor. It can inhibit the metabolism of oral or inhaled corticosteroids, producing cortisol excess leading to Cushing's syndrome and adrenal insufficiency. An assessment of causality indicated a possible adverse interaction between itraconazole and budesonide. CONCLUSIONS: The combination of itraconazole and inhaled corticosteroids is increasingly being used to treat conditions such as allergic bronchopulmonary aspergillosis. Clinicians need to be aware of the potential for an interaction between such a combination.

Administration, Inhalation↗
PubMed2003

Bilateral femoral head osteonecrosis after septic shock and multiorgan failure.

UNLABELLED: A case of bilateral femoral head osteonecrosis after septic shock is presented. We suggest that the osteonecrosis was caused by ischemic insults to the proximal femora. The association between septic shock and osteonecrosis has not been previously reported. INTRODUCTION: Osteonecrosis is an uncommon disorder characterized by the in situ death of bone. A diverse range of conditions has been associated with osteonecrosis. We present a case of bilateral femoral head osteonecrosis that occurred after an episode of septic shock. MATERIALS AND METHODS: A 66-year-old woman presented with a left-sided renal stone and a urinary tract infection. Her condition rapidly progressed to a life-threatening illness with septic shock complicated by multiorgan failure, which necessitated prolonged intensive care and inotropic support. She made a full recovery but 3 months later developed bilateral osteonecrosis of the femoral heads requiring bilateral total hip joint replacement. RESULTS AND CONCLUSIONS: We propose that the osteonecrosis was caused by ischemic insults to the femoral heads as a result of the widespread systemic ischemia that occurred during her initial illness. To our knowledge, septic shock has not been previously described as a cause of osteonecrosis. Clinicians should be aware of this association, particularly in patients presenting with bone pain after episodes of sepsis.

Adrenal Cortex Hormones↗