Daily nasal spray of hPTH(1–34) for 3 months increases bone mass in osteoporotic subjects: a pilot study

Introduction Although intermittent parathyroid hormone (PTH) injection can lead to strong anabolic effects on bone, daily subcutaneous injection is a disadvantage for patient acceptance. We have developed a nasal spray formula of parathyroid peptide [hPTH(1–34)] with peak serum hPTH(1–34) concentrations by nasal spray of 1,000 μg similar to those by subcutaneous injections of 20 μg hPTH(1–34).Methods To determine the clinical efficacy and safety of nasal hPTH(1–34) spray, a randomized, open-labeled clinical trial was conducted in subjects with osteoporosis. Ninety osteoporotic subjects age 52–84 years (mean 66.5 years) were randomly assigned to receive either 250 μg (PTH250, n=31), 500 μg (PTH500, n=30), or 1,000 μg (PTH1000, n=29) of daily nasal hPTH(1–34) spray for 3 months. All received daily supplements of 300 mg calcium and 200 IU vitamin D₃.Results Daily nasal hPTH(1–34) spray for 3 months increased lumbar bone mineral density (L-BMD) in a dose-dependent manner, and the PTH1000 group showed a 2.4% increase in L-BMD from baseline. Only the 1,000-μg dose produced consistent and statistically significant changes in markers of bone turnover; after 3 months, median serum type I procollagen N-propeptide (PINP) and osteocalcin increased 14.8% and 19.4% from baseline, while urinary type I collagen N-telopeptide (NTX) decreased 16.4%. Seven subjects developed transient hypercalcemia at 3 h after nasal hPTH(1–34) spray, but none of the subjects developed sustained hypercalcemia.Conclusion These observations demonstrate that nasal hPTH(1–34) spray is safe and well tolerated and can rapidly increase L-BMD. The results warrant further studies to examine its long-term efficacy on bone mass and fractures.