Abstract
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▴ Full-length parathyroid hormone (PTH) 1–84 is a recombinant version of human PTH. It is approved in the EU for the treatment of postmenopausal women with osteoporosis who have a high risk of fractures. Once-daily subcutaneous administration of PTH(1–84) stimulates new bone formation and increases bone mass.
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▴ In the pivotal, randomised, double-blind, multicentre, 18-month TOP trial in 2532 postmenopausal women with osteoporosis, subcutaneous PTH(1–84) 100 μg/day significantly reduced the incidence of new or worsened vertebral fractures relative to placebo (primary endpoint). Moreover, the increase from baseline in bone mineral density (BMD) at the lumbar spine, total hip, femoral neck and trochanter was also significantly greater than in the placebo group.
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▴ In another well designed study (PaTH; n = 238), 1 year of subcutaneous PTH(1–84) 100 μg/day followed by 1 year of alendronate 10 mg/day resulted in significantly greater increases in total spine, femoral neck and total hip BMD at 24 months compared with patients who received placebo for the second year. During the first year, PTH(1–84) in combination with alendronate was no more effective than PTH(1–84) monotherapy in terms of increasing areal lumbar spine BMD.
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▴ PTH(1–84) is generally well tolerated, although patients should be monitored for elevated serum calcium.
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References
Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 2005 Dec; 115 (12): 3318–25
Delmas PD, Rizzoli R, Cooper C, et al. Treatment of patients with postmenopausal osteoporosis is worthwhile. The position of the International Osteoporosis Foundation. Osteoporos Int 2005 Jan; 16 (1): 1–5
McClung M. Parathyroid hormone for the treatment of osteoporosis. Obstet Gynecol Surv 2004; 59 (12): 826–32
Murray TM, Rao LG, Divieti P, et al. Parathyroid hormone secretion and action: evidence for discrete receptors for the carboxyl-terminal region and related biological actions of carboxyl-terminal ligands. Endocr Rev 2005 Feb; 26 (1): 78–113
Potts JT. Parathyroid hormone: past and present. J Endocrinol 2005 Dec; 187 (3): 311–25
Carter PH, Schipani E. The roles of parathyroid hormone and calcitonin in bone remodeling: prospects for novel therapeutics. Endocr Metab Immune Disord Drug Targets 2006 Mar; 6 (1): 59–76
Whitfield JF, Morley P, Willick GE. Parathyroid hormone, its fragments and their analogs for the treatment of osteoporosis. Treat Endocrinol 2002; 1 (3): 175–90
Nycomed. Preotact (full-length parathyroid hormone): product information (EU) [online]. Available from URL: http://www.emea.eu.int/humandocs/Humans/EPAR/preotact/preotactM.htm [Accessed 2006 May 31]
Schwietert HR, Groen EWJ, Sollie FAE, et al. Single-dose subcutaneous administration of recombinant human parathyroid hormone [rhPTH(1–84)] in healthy postmenopausal volunteers. Clin Pharmacol Ther 1997 Mar; 61: 360–76
Groen EWJ, Schwietert HR, Van Marie SP, et al. Multiple dose administration of recombinant human parathyroid hormone (rhPTH (1–84)) in healthy postmenopausal volunteers [abstract no. 525]. Therapie 1995; 50 Suppl.
Hodsman AB, Hanley DA, Ettinger MP, et al. Efficacy and safety of human parathyroid hormone-(1–84) in increasing bone mineral density in postmenopausal osteoporosis. J Clin Endocrinol Metab 2003 Nov; 88 (11): 5212–20
Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003 Sep 25; 349 (13): 1207–15
Moreau IA, Smith SY, Guldberg RE, et al. Treatment of osteopenic rhesus monkeys with parathyroid hormone 1–84 for 16 months improves vertebral trabecular bone quantity and quality [abstract no. M415]. J Bone Miner Res 2005 Sep; 20 Suppl. 1: S412
Kimmel DB, Bozzato RP, Kronis KA, et al. The effect of recombinant human (1–84) or synthetic human (1–34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats. Endocrinology 1993 Apr; 132 (4): 1577–84
Whitfield JF, Morley P, Willick GE, et al. Comparison of the ability of recombinant human parathyroid hormone, rhPTH-(1–84), and hPTH-(1–31)NH2 to stimulate femoral trabecular bone growth in ovariectomized rats. Calcif Tissue Int 1997 Jan; 60 (1): 26–9
Ejersted C, Andreassen TT, Oxlund H, et al. Human parathyroid hormone (1–34) and (1–84) increase the mechanical strength and thickness of cortical bone in rats. J Bone Miner Res 1993 Sep; 8 (9): 1097–101
Samnegard E, Iwaniec UT, Cullen DM, et al. Maintenance of cortical bone in human parathyroid hormone(1–84)-treated ovariectomized rats. Bone 2001 Mar; 28 (3): 251–60
NPS Pharmaceuticals. NPS reports positive PREOS study results [online]. Available from URL: http://www.npsp.com [Accessed 2006 Jun 14]
Fox J, Smith S, Jolette J, et al. A no observable carcinogenic effect dose level identified in Fischer 344 rats following daily treatment with PTH(1–84) for 2 years: role of the c-terminal PTH receptor? 33rd European Symposium on Calcified Tissues; 2006 May 10–14; Prague
Vahle JL, Sato M, Long GG, et al. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1–34) for 2 years and relevance to human safety. Toxicol Pathol 2002 May–Jun; 30 (3): 312–21
Eli Lilly and Company. Forteo teriparatide (rDNA origin) injection: prescribing information (US) [online]. Available from URL: http://www.fda.gov [Accessed 2006 Jun 14]
Greenspan SL, Bone HG, Marriott TB, et al. Preventing the first vertebral fracture in postmenopausal women with low bone mass using PTH(1–84): results from the TOP study [abstract no. 1222]. J Bone Miner Res 2005 Sep; 20 Suppl. 1: S56
Miller PD. PTH(1–84) prevents vertebral fractures in post menopausal women with higher fracture risk: results from the TOP study [abstract no. P425]. 33rd European Symposium on Calcified Tissues; 2006 May 10–14; Prague
Bogado CE, Zanchetta JR, Mango A, et al. Effects of parathyroid hormone 1–84 on cortical and trabecular bone at the hip as assessed by QCT: results at 18 months from the TOP Study [abstract no. 1083]. J Bone Miner Res 2005 Sep; 20 Suppl. 1: S22
Bogado CE, Zanchetta JR, Gordon CL, et al. Treatment of postmenopausal osteoporotic women with parathyroid hormone (1–84) for 18 months decreases BMD but does not affect indices of bone strength at the distal radius [abstract no. F383]. J Bone Miner Res 2006; 21 Suppl. 1
Ettinger MP, Marriott TB. Recombinant human parathyroid hormone 1–84 (PTH) reduces the incidence of multiple new vertebral fractures and new fracture severity in postmenopausal osteoporotic women [abstract no. P321MO]. Osteoporos Int 2006; 17 Suppl. 2: S90
Greenspan SL, Marriott TB, Hanley DA, et al. Full-length PTH prevents first vertebral fracture in postmenopausal women with osteoporosis: results from the TOP study [abstract]. 5th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis; 2005 Mar 16–19; Rome
Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 2005 Aug 11; 353 (6): 555–65
Fogelman I, Christiansen C, Spector T, et al. Safety and efficacy of PTH(1–84) at 18 and 24 months in women with postmenopausal osteoporosis receiving hormone therapy: results from the POWER study [abstract no. 1080]. J Bone Miner Res 2005 Sep; 20 Suppl. 1: S21–2
European Medicines Agency. Scientific discussion (Preotact) [online]. Available from URL: http://www.emea.eu.int/humandocs/PDFs/EPAR/preotact/PreotactEparScientificDen.pdf [Accessed 2006 May 31]
Greenspan SL, Hanley DA, Morris S, et al. Bone turnover markers and BMD remain elevated in postmenopausal osteoporotic women through a full 24 months of treatment with human parathyroid hormone 1–84 (PTH) [abstract no. F389]. 28th Annual Meeting of the American Society for Bone and Mineral Research; 2006 Sep 15–19; Philadelphia (PA)
Data on file. Nycomed, 2006
Compston J, Silverman S, Mathisen A, et al. Parathyroid hormone (1–84) is effective in patients with a wide range of clinical risk factors [abstract no. OP0126]. 2006 Annual European Congress of Rheumatology; 2006 Jun 21–24; Amsterdam
Fox J, Miller MA, Recker RR, et al. Treatment of postmenopausal osteoporotic women with parathyroid hormone 1–84 for 18 months increases cancellous bone formation and improves cancellous architecture: A study of iliac crest biopsies using histomorphometry and micro computed tomography. J Musculoskelet Neuronal Interact 2005 Dec; 5 (4): 356–7
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Moen, M.D., Scott, L.J. Recombinant Full-Length Parathyroid Hormone (1–84). Drugs 66, 2371–2381 (2006). https://doi.org/10.2165/00003495-200666180-00008
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DOI: https://doi.org/10.2165/00003495-200666180-00008