Two Cases of Improved Bone Mineral Density Following Treatment of Hypophosphatemic Osteomalacia Due to FGF23 Excess.

Excess fibroblast growth factor-23 (FGF23) causes renal phosphorous wasting and impaired activation of vitamin D leading to osteomalacia. Tumor-induced osteomalacia (TIO) is a rare cause of FGF23-mediated hypophosphatemia. We present 2 patients with FGF23-mediated hypophosphatemia who had low bone mineral density (BMD) at diagnosis and remarkable improvements in BMD with treatment. Patient 1 is a 43-year-old man who had years of progressive pain, difficulty ambulating, and multiple fractures. Patient 2 is a 48-year-old nonverbal man with autism and intellectual disability who had months of progressively declining mobility, presumed pain, and multiple fractures. Workup in both cases revealed hypophosphatemia, evidence of renal phosphorous wasting, and elevated FGF23. Patient 1 was diagnosed with TIO when imaging identified a subcutaneous left flank mass and excision resulted in rapid symptom improvement; he experienced a 96% increase in lumbar spine (LS) BMD after surgery. Patient 2 has had multiple scans over several years, but no FGF23-secreting tumor has been identified. He has been maintained on medical treatment with phosphorous and calcitriol with improvement in functioning and 48% increase in LS BMD. Both patients had improvements in BMD with treatment, with more pronounced improvement in the patient with TIO managed surgically.

Bone Mineral Density During and After Lactation: A Comparison of African American and Caucasian Women.

During lactation, changes in maternal calcium metabolism are necessary to provide adequate calcium for newborn skeletal development. The calcium in milk is derived from the maternal skeleton through a process thought to be mediated by the actions of parathyroid hormone-related protein (PTHrP) in combination with decreased circulating estrogen concentrations. After weaning, bone lost during lactation is rapidly regained. Most studies of bone metabolism in lactating women have been performed in Caucasian subjects. There are well-documented differences between African American (AA) and Caucasian (C) bone metabolism, including higher bone mineral density (BMD), lower risk of fracture, lower 25-hydroxyvitamin D (25(OH) D), and higher PTH in AA compared to C. In this prospective paired cohort study, BMD and markers of bone turnover were compared in self-identified AA and C mothers during lactation and after weaning. BMD decreased in both AA and C women during lactation, with similar decreases at the lumbar spine (LS) and greater bone loss in the C group at the femoral neck (FN) and total hip (TH), demonstrating that AA are not resistant to PTHrP during lactation. BMD recovery compared to the 2 week postpartum baseline was observed 6 months after weaning, though the C group did not have complete recovery at the FN. Increases in markers of bone formation and resorption during lactation were similar in AA and C. C-terminal telopeptide (CTX) decreased to 30% below post-pregnancy baseline in both groups 6 months after weaning, while procollagen type 1 N-terminal (P1NP) returned to baseline in the AA group and fell to below baseline in the C group. Further investigation is required to determine impacts on long term bone health for women who do not fully recover BMD before a subsequent pregnancy.

SAFETY AND EFFICACY OF A PERI-OPERATIVE PROTOCOL FOR PATIENTS WITH DIABETES TREATED WITH CONTINUOUS SUBCUTANEOUS INSULIN INFUSION WHO ARE ADMITTED FOR SAME-DAY SURGERY.

OBJECTIVE: The number of people with diabetes using continuous subcutaneous insulin infusions (CSII) with an insulin pump has risen dramatically, creating new challenges when these patients are admitted to the hospital for surgical or other procedures. There is limited literature guiding CSII use during surgical procedures. METHODS: The study was carried out in a large, urban, tertiary care hospital. We enrolled 49 patients using insulin pump therapy presenting for 57 elective surgeries. We developed a CSII peri-operative glycemic management protocol (PGMP) to standardize insulin pump management in patients admitted to a same-day surgery unit (SDSU). The purpose was evaluate the safety (% capillary blood glucose (CBG) <70 mg/dL and/or pump incidents) and efficacy (first postoperative CBG ≤200 mg/dL) of the CSII PGMP. We determine the contribution of admission CBG, type of anesthesia, surgery length, and peri-operative steroid use on postoperative glycemic control. RESULTS: Overall, 63% of patients treated according to the CSII PGMP had a first postoperative CBG ≤200 mg/dL. There were no episodes of intra- or postoperative hypoglycemia. For patients treated with the CSII PGMP, the mean postoperative CBG was lower in patients with anticipated or actual surgical length ≤120 minutes (158.1 ± 53.9 vs. 216 ± 77.7 mg/dL, P<.01). No differences were observed with admission CBG, type of anesthesia, or steroid use. CONCLUSIONS: This study demonstrates that a CSII PGMP is both safe and effective for patients admitted for elective surgical procedures and provides an example of a standardized protocol for use in clinical practice.

Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis.

Osteoporotic fractures result in significant morbidity and mortality. Anabolic agents reverse the negative skeletal balance that characterizes osteoporosis by stimulating osteoblast-dependent bone formation to a greater degree than osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP) are peptide hormones, which have anabolic actions when administered intermittently. The only FDA-approved anabolic bone agent for the treatment of osteoporosis in the United States is PTH 1-34, or teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog, BA058, have also been shown to increase lumbar spine bone density. These agents and several other PTH and PTHrP analogs, including some which are not administered as injections, continue to be investigated as potential anabolic therapies for osteoporosis.

A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study.

Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 µg/day; PTHrP(1-36) 600 µg/day; and PTH(1-34) 20 µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p < 0.05) at the TH and for PTHrP(1-36) 400 (p < 0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2 D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia. Longer-term studies using lower doses of PTHrP(1-36) are needed to define both the optimal dose and full clinical benefits of PTHrP. © 2013 American Society for Bone and Mineral Research.