Use of depot medroxyprogesterone acetate and fracture risk

Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited.; We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk.; We conducted a case-control analysis using the United Kingdom-based General Practice Research Database.; Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008.; Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders.; We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (<2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1.; This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures

A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.

PurposeIn 2012 we reported in six individuals a clinical condition almost indistinguishable from PLOD1-kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS), caused by biallelic mutations in FKBP14, and characterized by progressive kyphoscoliosis, myopathy, and hearing loss in addition to connective tissue abnormalities such as joint hypermobility and hyperelastic skin. FKBP14 is an ER-resident protein belonging to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases); it catalyzes the folding of type III collagen and interacts with type III, type VI, and type X collagens. Only nine affected individuals have been reported to date.MethodsWe report on a cohort of 17 individuals with FKBP14-kEDS and the follow-up of three previously reported patients, and provide an extensive overview of the disorder and its natural history based on clinical, biochemical, and molecular genetics data.ResultsBased on the frequency of the clinical features of 23 patients from the present and previous cohorts, we define major and minor features of FKBP14-kEDS. We show that myopathy is confirmed by histology and muscle imaging only in some patients, and that hearing impairment is predominantly sensorineural and may not be present in all individuals.ConclusionOur data further support the extensive clinical overlap with PLOD1-kEDS and show that vascular complications are rare manifestations of FKBP14-kEDS

Automated HPLC assay for urinary collagen cross-links: effect of age, menopause, and metabolic bone diseases

BACKGROUND: The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. METHODS: We used a commercially available reagent set (Chromsystems Instruments ; Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). RESULTS: The mean intraassay and interassay CVs were >6% and >8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20-49 years. In men, cross-link values peaked at 20-29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%-60% at age 11-14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. CONCLUSIONS: The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases

Primärer Hyperparathyreoidismus

Primary hyperparathyroidism is frequently an incidental finding in asymptomatic patients. Often the diagnosis of primary hyperparathyroidism is made in evaluation for osteoporosis, rarely in the context of hypercalcemic crisis, myopathy, kidney stones, nephrocalcinosis, and osteitis fibrosa. The most frequent cause for primary hyperparathyroidism is benign parathyroid adenoma, reminders have hyperplasia. Primary hyperparathyroidism is defined as hypercalcemia with inappropriately high parathyroid hormone levels. Surgery is the definitive treatment for patients with symptomatic primary hyperparathyroidism and asymptomatic patients, who meet one of the following criteria: serum calcium 60 ml/min) and presence of osteoporosis (T-score > – 2.5 or fracture). Parathyroidectomy should be performed by an experienced surgeon. As an alternative in inoperable patients or preoperatively in severe hypercalcemia cinacalcet successfully reduces calcium levels. In asymptomatic patients not meeting the above mentioned criteria serum calcium and creatinin levels should be measured once a year and DXA every two years, since 30 % of the patients with asymptomatic primary hyperparathyroidism are progressive

Proton pump inhibitors and fracture risk: true effect or residual confounding?

Fracture is a major contributor to human morbidity and mortality, especially in the elderly. It has been discussed in the literature that conditions associated with decreased stomach acidity may lead to a decrease in intestinal calcium absorption and, consequently, to an increased fracture risk. In recent years, several observational studies reported a slightly increased fracture risk in association with the use of proton pump inhibitors (PPIs) and/or histamine H(2) receptor antagonists. It was the objective of this review to critically assess the available evidence linking PPI use to an increased fracture risk. A MEDLINE and EMBASE search from 1960 to June 2010 was performed to identify the relevant articles using predefined search terms. Because (i) there is no proven mechanism, (ii) the reported magnitude of the risk elevation associated with the use of PPIs was only weak, and (iii) the likelihood of residual confounding despite adjustment for known co-morbidities and drug use cannot be ruled out, we conclude that the currently available literature does not support the notion that the use of PPIs is causally related to a materially increased fracture risk in humans