title: Daily nasal spray of hPTH(1-34) for 3 months increases bone mass in osteoporotic subjects: a pilot study.
abstract: BACKGROUND
  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 microg similar to those by subcutaneous injections of 20 microg 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 microg (PTH250, n=31), 500 microg (PTH500, n=30), or 1,000 microg (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 D(3).
  
  
  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-microg 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Health Biosciences, Tokushima, 770-8503, Japan. toshimat@clin.med.tokushima-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Shiraki
authors.forename: H
authors.initials: H
authors.lastname: Hagino
authors.forename: H
authors.initials: H
authors.lastname: Iinuma
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000281:Administration, Intranasal; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D010349:Patient Compliance; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D011347:Procollagen / Q000097:blood; D019379:Teriparatide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D019379:Teriparatide