Risk factors for fracture in adult kidney transplant recipients.

AIM: To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients. METHODS: We conducted a cohort study of all adults who received a kidney-only transplant (n = 2723) in Ontario, Canada between 2002 and 2009. We used multivariable Cox proportional hazards regression to determine general and transplant-specific risk factors for major fractures (proximal humerus, forearm, hip, and clinical vertebral). The final model was established using the backward elimination strategy, selecting risk factors with a P-value ≤ 0.2 and forcing recipient age and sex into the model. We also assessed risk factors for other fracture locations (excluding major fractures, and fractures involving the skull, hands or feet). RESULTS: There were 132 major fractures in the follow-up (8.1 fractures per 1000 person-years). General risk factors associated with a greater risk of major fracture were older recipient age [adjusted hazard ratio (aHR) per 5-year increase 1.11, 95%CI: 1.03-1.19] and female sex (aHR = 1.81, 95%CI: 1.28-2.57). Transplant-specific risk factors associated with a greater risk of fracture included older donor age (5-year increase) (aHR = 1.09, 95%CI: 1.02-1.17) and end-stage renal disease (ESRD) caused by diabetes (aHR = 1.72, 95%CI: 1.09-2.72) or cystic kidney disease (aHR = 1.73, 95%CI: 1.08-2.78) (compared to glomerulonephritis as the reference cause). Risk factors across the two fracture locations were not consistent (major fracture locations vs other). Specifically, general risk factors associated with an increased risk of other fractures were diabetes and a fall with hospitalization prior to transplantation, while length of time on dialysis, and renal vascular disease and other causes of ESRD were the transplant-specific risk factors associated with a greater risk of other fractures. CONCLUSION: Both general and transplant-specific risk factors were associated with a higher risk of fractures in kidney transplant recipients. Results can be used for clinical prognostication.

The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study.

STUDY QUESTION: Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture? METHODS: Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147,084 men aged ≥ 66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure. STUDY ANSWER AND LIMITATIONS: The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥ 66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs. WHAT THIS STUDY ADDS: Prostate-specific α antagonists are associated with a small but significant increased risk of fall, fracture, and head trauma, probably as a result of induced hypotension. FUNDING, COMPETING INTERESTS, DATA SHARING: This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site through the Kidney, Dialysis, and Transplantation (KDT) research program. BW has received a research grant from Astellas, and L-AF does consultancy for Amgen.

Osteoporotic fractures in patients with untreated hyperprolactinemia vs. those taking dopamine agonists: A systematic review and meta-analysis.

OBJECTIVE: Hyperprolactinemia is associated with bone fragility. Traditionally attributed to prolactin-induced hypogonadism, recent studies have identified increased fracture rates independent of gonadal function. METHODS: We performed a systematic review to identify studies assessing fracture risk in patients with untreated hyperprolactinemia compared to those on dopamine agonists. MEDLINE, EMBASE, Cochrane, Web of Science and BIOSIS Previews databases were searched from inception to December 2013 for studies of hyperprolactinemia with fractures as an outcome. Two authors independently performed title and abstract searches, full-text searches, data abstraction, and quality assessment. A summary odds ratio (OR) was calculated using a random effects model. RESULTS: Of the 197 articles identified, 2 met inclusion criteria. Both cross-sectional studies examined cabergoline use (or non-use) in patients with prolactin-secreting adenomas, with vertebral fractures as the primary outcome. For women, vertebral fractures were identified in 46% of untreated patients, vs. 20% of patients on cabergoline (OR: 0.29, 95% CI: 0.10-0.78). For men, the results were 67% in untreated, vs. 26% in cabergoline treated patients (OR: 0.18, CI: 0.03-0.94), with no difference between gonadal and hypogonadal men (p=0.8). Combining studies gave a summary odds ratio of 0.25 (CI: 0.11-0.59), I2=0%. CONCLUSIONS: In the limited studies available, fracture prevalence was increased in patients with untreated hyperprolactinemia compared to those on treatment, independent of gonadal function. Further studies are needed to clarify if post-menopausal women, or high-risk men, with no other indication for treatment, should be on dopamine agonists to decrease fracture risk.

Cardiac pheochromocytoma presenting during pregnancy.

A 25-year-old woman presented at 12 weeks gestation, with symptoms and laboratory investigations consistent with pheochromocytoma. Imaging modalities available during pregnancy were limited and MRI scan of the abdomen and the neck failed to localise the tumour. Postpartum imaging, including 131-metaiodobenzylguanidine and octreotide scans, cardiac CT, cardiac MRI and cardiac catheterisation, allowed accurate localisation of the tumour and helped plan for successful surgical removal.

Risk factors for idiopathic intracranial hypertension in men: a case-control study.

OBJECTIVE: To identify risk factors for idiopathic intracranial hypertension (IIH) in men. DESIGN: Case-control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis. SETTING: Outpatient clinics in two US tertiary care centers. PARTICIPANTS: The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category. MAIN OUTCOME MEASURES: Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel-Haenszel odds ratios and mixed-effects logistic regression models accounted for matching. RESULTS: Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6-54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5-12.9; p=0.03). CONCLUSIONS: Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men.

Glucocorticoid-induced osteoporosis: treatment update and review.

Glucocorticoid-induced osteoporosis (GIO) is a serious consequence of glucocorticoid therapy leading to fractures in 30-50% of patients. A wide range of protective medications have been studied in this condition including calcium, vitamin D, vitamin D analogs, oral and intravenous bisphosphonates, sex hormones, anabolic agents and calcitonin. The mechanism of action, and evidence for these therapies, are reviewed - focusing on important trials and new evidence. Recently published guidelines are also reviewed and compared. Bisphosphonates are currently the recommended first-line therapy for the prevention and treatment of GIO. They have been shown to increase bone mineral density (BMD) at the spine and hip and to decrease the incidence of vertebral fractures (especially in postmenopausal women). Testosterone therapy and female hormone replacement therapy (HRT) have been found to increase lumbar spine BMD in hypogonadal patients on glucocorticoid therapy, but effects on hip BMD have not been consistent and there is no fracture data in the GIO population. Similarly, calcitonin increases lumbar spine BMD but has no proven fracture efficacy. The effect of selective estrogen receptor modulators, the oral contraceptive pill and strontium on GIO is relatively unknown. Parathyroid hormone (PTH 1-34) and zoledronic acid have emerged as exciting new options for the treatment of GIO. Both therapies have been found to result in gains in BMD at the spine and hip that are either noninferior or superior to those seen with oral bisphosphonate therapy. PTH 1-34 has also been found to decrease the incidence of new vertebral fractures and may be an option in high-risk patients established on long-term glucocorticoid therapy.