Bone imaging in hypoparathyroidism.

Hypoparathyroidism (HypoPT) is an uncommon endocrine disorder characterized by chronic deficiency or absence of parathyroid hormone (PTH), which leads to a profound reduction in bone remodeling. Subjects with HypoPT typically have bone mineral densities (BMDs) by dual-energy X-ray absorptiometry (DXA) above average at all skeletal sites, with greatest scores observed at the lumbar spine. Trabecular bone score (TBS), an indirect measure of bone microarchitecture, also appears to be normal in HypoPT. By peripheral quantitative computed tomography (pQCT) of the radius, volumetric BMD at cancellous and cortical compartments, as well as cortical area and thickness, are greater in hypoparathyroid subjects than in controls. The use of high-resolution pQCT (HRpQCT) confirmed the increase in cortical volumetric BMD but demonstrated reduced cortical thickness, associated with lower cortical porosity in HypoPT. Trabeculae tend to be more numerous but thinner in hypoparathyroid subjects. It is not clear whether these structural and the dynamic skeletal abnormalities in HypoPT affect bone strength or fracture risk. Treatment of HypoPT with PTH leads to improvement in bone remodeling rate, variable changes in bone density, and a transient increase in estimated bone strength. The effect of PTH therapy on fracture risk remains unknown. This article reviews skeletal involvement and the effect of PTH treatment in patients with HypoPT, as assessed by DXA, TBS, QCT, and HRpQCT. Data on bone strength and fracture risk in HypoPT are also reviewed here.

Correlation between 25-hydroxyvitamin D levels and latitude in Brazilian postmenopausal women: from the Arzoxifene Generations Trial.

SUMMARY: We investigated vitamin D status in Brazilian cities located at different latitudes. Insufficiency (<50 nmol/L) was common (17 %), even in those living in a tropical climate. Vitamin D insufficiency increased as a function of latitude. Mean 25-hydroxyvitamin D (25(OH)D) levels in each site and latitude correlation were very high (r = -0.88; p=0.02). [corrected]. INTRODUCTION: Inadequate vitamin D, determined by low levels of 25(OH)D, has become very common despite the availability of sunlight at some latitudes. National data from a country that spans a wide range of latitudes would help to determine to what extent latitude or other factors are responsible for vitamin D deficiency. We investigated vitamin D status in cities located at different latitudes in Brazil, a large continental country. METHODS: The source is the Brazilian database from the Generations Trial (1,933 osteopenic or osteoporotic postmenopausal women (60 to 85 years old) with 25(OH)D measurements). 25(OH)D below 25 nmol/L (10 ng/mL) was an exclusion criterion. Baseline values were between fall and winter. The sites included Recife, Salvador, Rio de Janeiro, São Paulo, Curitiba, and Porto Alegre. Mean and standard deviation of 25(OH)D, age, spine and femoral neck T-score, calcium, creatinine, and alkaline phosphatase were calculated for each city. Pearson correlation was used for 25(OH)D and latitude. RESULTS: Insufficiency (<50 or <20 ng/mL) was common (329 subjects, 17 %). Vitamin D insufficiency increased as a function of latitude, reaching 24.5 % in the southernmost city, Porto Alegre. The correlation between mean 25(OH)D levels in each site and latitude was very high (r = -0.88, p < 0.0001). CONCLUSION: There is a high percentage of individuals with vitamin D insufficiency in Brazil, even in cities near the equator, and this percentage progressively increases with more southern latitudes.

A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients.

AIM: The purpose of this study was to evaluate if superior glycaemic control could be achieved with Avandamet® (rosiglitazone/metformin/AVM) compared with metformin (MET) monotherapy, and if glycaemic effects attained with AVM are durable over 18 months of treatment. Bone mineral density (BMD) and bone biomarkers were evaluated in a subgroup of patients. METHODS: This was a phase IV, randomized, double-blind, multi-centre study in 688, drug naÏve, male and female patients who had an established clinical diagnosis of type 2 diabetes mellitus (T2DM). Patients were randomized in a 1 : 1 ratio either to AVM or MET. RESULTS: As initial therapy in patients with T2DM, AVM was superior to MET in achieving statistically significant reductions in glycated haemoglobin (HbA1c) (p < 0.0001) and fasting plasma glucose (FPG) (p < 0.001), with more patients reaching recommended HbA1c and FPG targets for intensive glycaemic control. The glycaemic effects attained with AVM compared to MET monotherapy were durable over 18 months of treatment. In the bone substudy, AVM was associated with a significantly lower BMD in comparison with MET at week 80 in the lumbar spine and total hip (p < 0.0012 and p = 0.0005, respectively). Between-treatment differences were not statistically significant for distal one-third of radius BMD, femoral neck BMD or total BMD. CONCLUSION: Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip.

Bone turnover 18 months after a single intravenous dose of zoledronic acid.

Zoledronic acid inhibits bone resorption for up to 12 months. It is not known whether the duration of this antiresorptive effect extends beyond this period of time. The aim of this study was to evaluate the changes in bone turnover at 12 months (T12) and 18 months (T18) after a single injection of 4 mg of zoledronic acid. It is a prospective, longitudinal study, with a follow-up for 18 months. We studied male and female patients (60.5 +/- 11.0 years old), with low bone mineral density (BMD) coming from the outpatient clinic in a metabolic bone unit of a tertiary care hospital. All patients received a single intravenous dose of 4 mg of zoledronic acid, bone turnover markers [serum carboxyterminal telopeptide of type I collagen (CTX-I), bone-specific alkaline phosphatase (BSAP)] and BMD [lumbar spine (LS) and total hip (TH)] were measured at baseline, and after 12 months (T12) and 18 months (T18). Median serum CTX-I and BSAP levels were suppressed at T12 in comparison with baseline values: 0.183 to 0.039 ng/ml for CTX-I (p = 0.0002) and 16.95 to 13.96 U/l for BSAP (p = 0.005). At T18, both CTX-I and BSAP continued to be suppressed below baseline at 0.108 ng/ml and 12.23 U/l (p = 0.009 and p = 0.02, vs. T0). Significant increases in BMD at T18 as compared with T12 were observed in patients (median increase 6.1% for LS and 2.0% for TH). Zoledronic acid inhibits bone turnover effectively for 12 months, with evidence for continued suppression and gains in BMD even after 18 months.

Bone mass measurement in identification of women at risk for osteoporosis.

It is now possible to measure bone mass with highly precise, safe and noninvasive technology. Dual energy X-ray absorptiometry (DXA) can detect bone loss well before it becomes evident by conventional X-rays or by fracture. Because measurement of bone density is the single most important predictor of fracture risk, it is a critically important tool to apply to the population at risk, which includes women who have definable risk factors for osteoporosis, such as the menopause, as well as those with a family history of osteoporosis, life-long low calcium intake, smoking, extreme thinness, anorexia, certain diseases and medications. Central DXA machines measure bone mass of the lumbar spine and hip region, the most important potential fracture sites. At the present time, the number of DXA machines in the United States is inadequate to detect the entire population at risk. Even if there were a sufficient number of DXA machines, lack of insurance reimbursement would limit their use. These restraints are beginning to be better defined, if not moderated, by the Bone Mass Measurement Act of 1998. With insufficient numbers of DXA machines and their heavy localization to major urban medical centers, peripheral devices have been developed. Using DXA technology, these peripheral devices can measure densities in the distal forearm, the middle phalangeal bone, and the heel. Ultrasound technology has also been developed to measure bone density of the tibia and the heel. The peripheral densitometers, in general, have the advantage of smaller size, lower cost, and portability. A very controversial issue, however, is whether measurement at a peripheral site provides sufficiently accurate information about bone mass at more important central sites to be generally reliable. Nevertheless, they have great potential in helping to detect the large numbers of women at risk for osteoporosis. Eventually, however, central measurements of bone mass will be needed, especially for monitoring of therapy, so that central measurements of bone mass by DXA are still the "gold standard" in the field at this time.