Faculty Bibliography

CONTEXT: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors that cause TIO and is, at least partly, responsible for the manifestations of TIO. OBJECTIVE: The objective of this study was to determine the sensitivity of FGF23 measurements in TIO. DESIGN: FGF23 concentrations were measured on stored samples with three ELISAs. SETTING: This study was conducted at subspecialty referral centers. PATIENTS: Twenty-two patients with suspected TIO, 13 with confirmed tumors, were studied. INTERVENTIONS: There were no interventions in this study. MAIN OUTCOME MEASURE: FGF23 concentration was the main outcome measure of this study. RESULTS: Elevated FGF23 concentrations were detected using the Immunotopics C-terminal assay in 16 of 22 TIO patients (for a sensitivity of 73%), the Immunotopics Intact assay in five of 22 patients (sensitivity, 23%), and the Kainos Intact assay in 19 of 22 patients (sensitivity, 86%). In the 13 patients with confirmed tumors, the sensitivity was higher with all assays: 92% for the Immunotopics C-terminal assay, 38% for the Immunotopics Intact assay, and 100% for the Kainos assay. CONCLUSION: The Kainos Intact assay was the most sensitive, followed by the Immunotopics C-terminal assay. The findings of normal FGF23 concentrations in some patients with TIO may indicate that FGF 23 is not responsible for the hypophosphatemia in these patients or that FGF23 secretion by some tumors is partially responsive to serum phosphate. Normal FGF23 concentrations should be interpreted in relation to the serum phosphate and 1,25-dihydryxyvitamin-D concentrations.

PURPOSE OF REVIEW: The female athlete triad - anorexia, athletics, and amenorrhea - is a clinical problem found among young women who are engaged in intense physical activity. This review describes the psychological factors involved in the triad and the endocrine and skeletal consequences of the disorder. This subject is particularly timely and important as eating disorders are increasing in frequency among young women athletes. RECENT FINDINGS: Concern about body weight and its effect on athletic performance can lead to chronic undernutrition. Complications of low body weight include hormonal disturbances, bone loss and fracture. The potential endocrine abnormalities seen in this group of women include anovulatory cycles, chronic elevation in glucocorticoids and lower serum leptin concentrations. Lower insulin-like growth factor-1 and resistance to growth hormone have also been described. Treatment of consequent bone loss with hormones, and most recently, with bisphosphonates, provides conflicting, but also encouraging data. SUMMARY: The pressures to improve peak athletic performance often underlie the abnormal behavior and eating disorders characteristic of the female athlete triad, with subsequent life-long consequences. Physicians should be made aware of such pressures, and their psychological and physical consequences. Prevention is the best medicine; but more research in ways to effectively and safely treat bone loss in young women is needed

Bisphosphonates have been approved in the US as oral medication for the treatment of osteoporosis for about 10 years. Efficacy data exists for fracture reduction for the commonly used oral bisphosphonates but not for intravenous formulations. Based on the mechanism of action that appears to allow for longer intervals between doses, it has been possible to extend the treatment choices from the original more demanding daily oral dose to an array of options including oral weekly and more recently monthly treatment (so-called cyclical therapy) and intravenous treatment with various administration regimens. The possibility of treatment with an annual (or less frequent) intravenous administration with zoledronic acid exists. Compliance, adverse effects, and efficacy vary with each administration regimen.

Therapy for osteoporosis is principally centered on the use of agents that block bone resorption and supplementation with vitamin D and calcium. Although these drugs are effective in reducing the risk of subsequent fractures, and modestly increasing bone density, most patients being treated for osteoporosis still have low bone mass and a greater risk of fracture. Anabolic agents stimulate bone formation, strength, and mass. In addition, there is emerging evidence that anabolic agents can reduce subsequent fracture risk. The two most promising agents, parathyroid hormone (PTH) and GH/IGF-I, act to increase osteoblast mediated bone formation. A review of the potential usefulness of PTH and GH/IGF-I is presented.