Intermittent and low-dose
parathyroid hormone (PTH) injection to stimulate bone formation has been used in the treatment of
osteoporosis. The N-terminal fragment 1-34 of PTH is quite similar in structure and function to
N-terminal PTH-related
protein (
PTHrP).
PTH(1-34) and
PTHrP also share a coreceptor, the
PTH/PTHrP receptor. Therefore, some studies have suggested that
PTHrP could effectively stimulate bone formation, similar to PTH. We used an ovariectomized (OVX) rat model of
osteoporosis to study the effects of
PTHrP(1-34) on bone metabolism by measuring bone mineral density (BMD), bone histomorphometrics, and biomechanical parameters. We found that
subcutaneous injection of
PTHrP(1-34) (40 or 80 μg/kg
body weight every day) in OVX rats increased lumbar and femoral BMD, improved bone biomechanical properties, enhanced bone strength, and promoted bone formation. We selected 40 μg/kg as the preferred therapeutic dose of
PTHrP(1-34) and investigated the effects of frequency of treatment (per 1, 2, 3, or 7 days) on bone metabolism in OVX rats. We found that injection of
PTHrP(1-34) once per day or every other day significantly improved the BMD and strength of OVX rats. Serum
calcium and
phosphate levels in all treated rats did not vary significantly from control rats. Based on our results, intermittent low-dose
PTHrP(1-34) injection promoted bone formation in OVX rats, suggesting a high potential for
therapeutic use in
osteoporosis patients.