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 treatment for 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.

Parathyroid hormone-related protein (PTHrP)(1–36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but has not been directly compared to parathyroid hormone (PTH)(1–34). We performed a three 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/d; PTHrP(1–36) 600 μg/d; and PTH(1–34) 20 μg/d. The primary outcomes 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)2vitamin 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 & 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)2D. 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.

Pediatric emergency department physicians can successfully partner with primary care physicians to implement national guidelines for children requiring maintenance antiinflammatory asthma therapy. Patient nonadherence continues to be a significant barrier for asthma management.

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