T Matsumoto1, M Shiraki, H Hagino, H Iinuma, T Nakamura. 1. 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
Abstract
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 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. 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.
RCT Entities:
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 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 procollagenN-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.
Authors: H Orimo; Y Hayashi; M Fukunaga; T Sone; S Fujiwara; M Shiraki; K Kushida; S Miyamoto; S Soen; J Nishimura; Y Oh-Hashi; T Hosoi; I Gorai; H Tanaka; T Igai; H Kishimoto Journal: J Bone Miner Metab Date: 2001 Impact factor: 2.626
Authors: Peiqi Chen; Julie H Satterwhite; Angelo A Licata; E Michael Lewiecki; Adrien A Sipos; Derek M Misurski; Rachel B Wagman Journal: J Bone Miner Res Date: 2005-01-18 Impact factor: 6.741
Authors: R M Neer; C D Arnaud; J R Zanchetta; R Prince; G A Gaich; J Y Reginster; A B Hodsman; E F Eriksen; S Ish-Shalom; H K Genant; O Wang; B H Mitlak Journal: N Engl J Med Date: 2001-05-10 Impact factor: 91.245
Authors: B Ettinger; D M Black; B H Mitlak; R K Knickerbocker; T Nickelsen; H K Genant; C Christiansen; P D Delmas; J R Zanchetta; J Stakkestad; C C Glüer; K Krueger; F J Cohen; S Eckert; K E Ensrud; L V Avioli; P Lips; S R Cummings Journal: JAMA Date: 1999-08-18 Impact factor: 56.272
Authors: D M Black; S R Cummings; D B Karpf; J A Cauley; D E Thompson; M C Nevitt; D C Bauer; H K Genant; W L Haskell; R Marcus; S M Ott; J C Torner; S A Quandt; T F Reiss; K E Ensrud Journal: Lancet Date: 1996-12-07 Impact factor: 79.321
Authors: Dennis M Black; Susan L Greenspan; Kristine E Ensrud; Lisa Palermo; Joan A McGowan; Thomas F Lang; Patrick Garnero; Mary L Bouxsein; John P Bilezikian; Clifford J Rosen Journal: N Engl J Med Date: 2003-09-20 Impact factor: 91.245
Authors: T Kohno; N Murasugi; H Sakurai; K Watabe; H Nakamuta; M Koida; Y Sugie; M Nomura; A Yanagawa Journal: J Clin Lab Anal Date: 1998 Impact factor: 2.352
Authors: Anthony B Hodsman; David A Hanley; Mark P Ettinger; Michael A Bolognese; John Fox; Anna J Metcalfe; Robert Lindsay Journal: J Clin Endocrinol Metab Date: 2003-11 Impact factor: 5.958
Authors: M Tezval; G Serferaz; T Rack; L Kolios; S Sehmisch; U Schmelz; H Tezval; K M Stuermer; E K Stuermer Journal: World J Urol Date: 2011-02-05 Impact factor: 4.226
Authors: M Tezval; E K Stuermer; S Sehmisch; T Rack; A Stary; M Stebener; F Konietschke; K M Stuermer Journal: Osteoporos Int Date: 2009-05-13 Impact factor: 4.507