Impact of pioglitazone on bone mineral density and bone marrow fat content.

Pioglitazone use is associated with an increased risk of fractures. In this randomized, placebo-controlled study, pioglitazone use for 12 months was associated with a significant increase in bone marrow fat content at the femoral neck, accompanied by a significant decrease in total hip bone mineral density. The change in bone marrow fat with pioglitazone use was predominantly observed in female vs. male participants. INTRODUCTION: Use of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood. This study aimed to assess the effect of pioglitazone treatment on femoral neck bone marrow (BM) fat content and on bone mineral density (BMD), and to establish if any correlation exists between the changes in these parameters. METHODS: In this double-blind placebo-controlled clinical trial, 42 obese volunteers with metabolic syndrome were randomized to pioglitazone (45 mg/day) or matching placebo for 1 year. The following measurements were conducted at baseline and during the treatment: liver, pancreas, and femoral neck BM fat content (by magnetic resonance spectroscopy), BMD by DXA, abdominal subcutaneous and visceral fat, and beta-cell function and insulin sensitivity. RESULTS: Results were available for 37 subjects who completed the baseline and 1-year evaluations. At 12 months, BM fat increased with pioglitazone (absolute change, +4.1%, p = 0.03), whereas BM fat content in the placebo group decreased non-significantly (-3.1%, p = 0.08) (p = 0.007 for the pioglitazone-placebo response difference). Total hip BMD declined in the pioglitazone group (-1.4%) and increased by 0.8% in the placebo group (p = 0.03 between groups). The change in total hip BMD was inversely and significantly correlated with the change in BM fat content (Spearman rho = -0.56, p = 0.01) in the pioglitazone group, but not within the placebo group (rho = -0.29, p = 0.24). Changes in BM fat with pioglitazone were predominantly observed in female vs. male subjects. CONCLUSIONS: Pioglitazone use for 12 months compared with placebo is associated with significant increase in BM fat content at the femoral neck, accompanied by a small but significant decrease in total hip BMD.

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday.

UNLABELLED: In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture. INTRODUCTION: A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants. METHODS: Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday. RESULTS: A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean ± SD age was 66.9 ± 8.9 years and BMI 24.5 ± 4.4 kg/m(2). Duration of bisphosphonate treatment was 5.2 ± 2.3 years, and follow-up during holiday was 3.3 ± 1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday. CONCLUSIONS: BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients. Additional studies are needed to identify predictors of fracture incidence during a bisphosphonate holiday.

Epidemiology of hip fractures in Lebanon: a nationwide survey.

INTRODUCTION: Hip fractures are a reliable indicator of osteoporosis. Despite their importance, few studies have assessed their epidemiology in Lebanon and the Middle East. HYPOTHESES: Hip fracture incidence rates in Lebanon approximate those of Northern countries, and show the same characteristics, particularly the exponential increase with age, higher incidence in women, and a recent trend of rate leveling in women but not in men. MATERIALS AND METHODS: A national database of hip fracture cases admitted to hospitals in Lebanon in 2007 was created. Crude and age-adjusted incidence rates were calculated at 5-year intervals for individuals over age 50. These rates were also standardized to the 2000 United States population, and compared to those of other countries. Projected incidence rates in Lebanon in 2020 and 2050 were also calculated. RESULTS: A total of 1199 patients were included in the study. The crude annual incidence rate in individuals over 50 was 147 per 100,000 individuals, 132 per 100,000 males and 160 per 100,000 females, with a female-to-male ratio of 1.2. The age-standardized annual incidence rates (per 100,000) were 180 in males and 256 in females. Assuming unchanged healthcare parameters, the projected crude incidence rates for people over 50 are expected to reach 174 and 284 per 100,000 in 2020 and 2050 respectively. CONCLUSIONS: Lebanese hip fracture rates are lower than Northern countries, but show many similar characteristics such as an exponential increase with age, a higher incidence in women, and clues of a leveling of rates in women but not in men. Numbers are expected to increase substantially in the coming decades. LEVEL OF EVIDENCE: Level IV. Epidemiological study.

The effects of smoking on bone metabolism.

Osteoporosis is a common, morbid and costly disorder characterized by deterioration in bone strength. Cigarette smoking is associated with reduced bone mineral density (BMD) and increased fracture risk. There are basic, clinical, and observational studies that define several of the underlying pathophysiologic mechanisms that predispose smokers to bone loss. Such mechanisms include alterations in calciotropic hormone metabolism and intestinal calcium absorption, dysregulation in sex hormone production and metabolism, alterations in adrenal cortical hormone metabolism and in the receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) system (RANK-RANKL-OPG system), and direct cellular effects of cigarette use on bone cells. In addition, there is evidence of reversibility in the aforementioned mechanisms with smoking cessation. In summary, cigarette smoking is a reversible risk factor for osteoporosis and osteoporotic fractures through diverse pathophysiologic mechanisms.

The spinal curvature irregularity index independently identifies vertebral fractures.

INTRODUCTION AND HYPOTHESIS: The spinal curvature irregularity index (SCII) is a quantitative measure of the irregularity of the spinal curvature. We evaluated the predictive ability of SCII to identify subjects with vertebral fractures (VF). METHODS: Vertebral heights were measured by quantitative vertebral morphometry in 461 Lebanese women 20-89 years of age and VFs were ascertained by the grade 1 Eastell method. SCII scores were log-transformed and expressed as Z-SCII, the number of standard deviations above or below the mean ln(SCII) of young patients without VF. Univariate and multivariate binary logistic regression models were used to identify clinical predictors of VF. RESULTS: Women with a higher SCII were more likely to have prevalent VF. A higher SCII was associated with a greater prevalence of VF within each category of femoral neck BMD (normal, osteopenia, osteoporosis). In univariate analysis, predictors of VF included Z-SCII (odds ratio, OR: 2.21, 95% CI: 1.80-2.71) and femoral neck T-score (OR: 1.35, 95% CI: 1.12-1.63). In multivariate analysis, predictors of VF were: Z-SCII (OR: 1.54, 95% CI: 1.02-2.32), femoral neck T-score (OR: 1.41, 95% CI: 1.11-1.78) and age(3) (OR: 1.40, 95% CI 1.10-1.82). At a cutoff SCII of 9.5%, the sensitivity and specificity of SCII for VF were 71 and 64% respectively, and higher SCII cutoffs identified VFs with greater specificity. CONCLUSION: The SCII is a robust, simple and independent indicator of the presence of VFs.