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Parathyroid hormone/parathyroid hormone-related protein analogs for osteoporosis

Clifford J Rosen, MD
Section Editor
Marc K Drezner, MD
Deputy Editor
Jean E Mulder, MD


The majority of osteoporosis medications (eg, bisphosphonates, denosumab, raloxifene, and estrogen) are antiresorptive agents that slow bone turnover, decrease bone resorption, and enhance bone mineral density (BMD), as more mineral is gradually deposited in older remodeling units. In contrast, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) analogs belong to a different class of anti-osteoporosis drugs called "anabolic" agents. There are fundamental differences in the mode of action of and skeletal response to PTH and PTHrP analogs compared with antiresorptive drugs [1].

This topic will review the use of PTH and PTHrP analogs as a therapy for osteoporosis. PTH physiology and other treatments for osteoporosis are reviewed in detail elsewhere. (See "Parathyroid hormone secretion and action" and "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)


In contrast to antiresorptive agents (eg, bisphosphonates, denosumab, raloxifene, and estrogen), PTH and PTHrP analogs stimulate bone formation and activate bone remodeling. Increases in bone formation occur more quickly than bone resorption, leading to an increase in lumbar bone mineral density (BMD) that is greater in the first two years of treatment than any antiresorptive agent.

PTH – Parathyroid hormone (PTH) is an 84-amino acid polypeptide secreted by the parathyroid glands in response to relatively small changes in serum calcium (figure 1). PTH is one of the three key hormones modulating calcium and phosphate homeostasis; the other two are calcitriol (1,25-dihydroxyvitamin D) and fibroblast growth factor 23 (FGF23). Through its actions to stimulate 1,25-dihydroxyvitamin D production, renal tubular calcium reabsorption, and bone resorption, PTH is responsible for maintaining serum ionized calcium concentrations within a narrow range. (See "Parathyroid hormone secretion and action".)

PTHrP – Parathyroid hormone-related protein (PTHrP) is produced in a wide variety of tissues and has diverse functions. It shares some of the actions of PTH, including stimulation of renal tubular calcium reabsorption and bone resorption, but it has minimal effect on intestinal calcium absorption, the latter due to weak stimulation of 1,25 dihydroxyvitamin D production. PTHrP also regulates cellular proliferation and is an important component of fetal calcium regulation, placental calcium transfer, and lactation [2,3]. PTHrP is produced by some cancers and is the primary cause of humeral hypercalcemia of malignancy. (See "Hypercalcemia of malignancy: Mechanisms", section on 'PTH-related protein'.)

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Literature review current through: Nov 2017. | This topic last updated: Jul 28, 2017.
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  1. Rosen CJ, Bilezikian JP. Clinical review 123: Anabolic therapy for osteoporosis. J Clin Endocrinol Metab 2001; 86:957.
  2. Simmonds CS, Kovacs CS. Role of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in regulating mineral homeostasis during fetal development. Crit Rev Eukaryot Gene Expr 2010; 20:235.
  3. Wysolmerski JJ. Parathyroid hormone-related protein: an update. J Clin Endocrinol Metab 2012; 97:2947.
  4. Hodsman AB, Bauer DC, Dempster DW, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005; 26:688.
  5. Hodsman A, Scientific Advisory Council of Osteoporosis Canada, Papaioannou A, et al. Clinical practice guidelines for the use of parathyroid hormone in the treatment of osteoporosis. CMAJ 2006; 175:48.
  6. Cranney A, Papaioannou A, Zytaruk N, et al. Parathyroid hormone for the treatment of osteoporosis: a systematic review. CMAJ 2006; 175:52.
  7. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208743 (Accessed on May 26, 2017).
  8. Hattersley G, Dean T, Corbin BA, et al. Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology 2016; 157:141.
  9. Cosman F, Nieves J, Zion M, et al. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 2005; 353:566.
  10. Fujita T, Inoue T, Morii H, et al. Effect of an intermittent weekly dose of human parathyroid hormone (1-34) on osteoporosis: a randomized double-masked prospective study using three dose levels. Osteoporos Int 1999; 9:296.
  11. Black DM, Bouxsein ML, Palermo L, et al. Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab 2008; 93:2166.
  12. Nakamura T, Sugimoto T, Nakano T, et al. Randomized Teriparatide [human parathyroid hormone (PTH) 1-34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk. J Clin Endocrinol Metab 2012; 97:3097.
  13. 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; 349:1207.
  14. Tashjian AH Jr, Chabner BA. Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women. J Bone Miner Res 2002; 17:1151.
  15. Greenspan SL, Bone HG, Ettinger MP, et al. Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 2007; 146:326.
  16. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344:1434.
  17. Miller PD, Hattersley G, Riis BJ, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA 2016; 316:722.
  18. 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; 353:555.
  19. Lindsay R, Scheele WH, Neer R, et al. Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 2004; 164:2024.
  20. Lane NE, Sanchez S, Modin GW, et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 2000; 15:944.
  21. Adami S, San Martin J, Muñoz-Torres M, et al. Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis. Osteoporos Int 2008; 19:87.
  22. Eastell R, Nickelsen T, Marin F, et al. Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS). J Bone Miner Res 2009; 24:726.
  23. Leder BZ, Tsai JN, Uihlein AV, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet 2015; 386:1147.
  24. Finkelstein JS, Hayes A, Hunzelman JL, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 2003; 349:1216.
  25. Finkelstein JS, Wyland JJ, Leder BZ, et al. Effects of teriparatide retreatment in osteoporotic men and women. J Clin Endocrinol Metab 2009; 94:2495.
  26. Cosman F, Nieves JW, Zion M, et al. Retreatment with teriparatide one year after the first teriparatide course in patients on continued long-term alendronate. J Bone Miner Res 2009; 24:1110.
  27. Cosman F, Miller PD, Williams GC, et al. Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial. Mayo Clin Proc 2017; 92:200.
  28. 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; 88:5212.
  29. Kakaria PJ, Nashel DJ, Nylen ES. Debilitating muscle cramps after teriparatide therapy. Ann Intern Med 2005; 142:310.
  30. 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; 30:312.
  31. Cipriani C, Irani D, Bilezikian JP. Safety of osteoanabolic therapy: a decade of experience. J Bone Miner Res 2012; 27:2419.
  32. Andrews EB, Gilsenan AW, Midkiff K, et al. The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res 2012; 27:2429.
  33. Jerome CP, Burr DB, Van Bibber T, et al. Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis). Bone 2001; 28:150.
  34. Misof BM, Roschger P, Cosman F, et al. Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 2003; 88:1150.
  35. Zanchetta JR, Bogado CE, Ferretti JL, et al. Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 2003; 18:539.
  36. Parfitt AM. Parathyroid hormone and periosteal bone expansion. J Bone Miner Res 2002; 17:1741.
  37. Dobnig H, Sipos A, Jiang Y, et al. Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab 2005; 90:3970.
  38. Kurland ES, Cosman F, McMahon DJ, et al. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000; 85:3069.
  39. Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 2003; 18:9.
  40. Lane NE, Sanchez S, Genant HK, et al. Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 2000; 11:434.
  41. Lindsay R, Nieves J, Formica C, et al. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997; 350:550.
  42. Chen P, Satterwhite JH, Licata AA, et al. Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 2005; 20:962.
  43. Rittmaster RS, Bolognese M, Ettinger MP, et al. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab 2000; 85:2129.
  44. Bogado CE, Zanchetta JR, Mango A, et al. Effects of parathyroid hormone I-84 on cortical and trabecular bone at the hip as assessed by QCT: Results at 18 months from the TOP study. J Bone Miner Res 2005; 20:S22.
  45. Cummings SR, Karpf DB, Harris F, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 2002; 112:281.
  46. Chen P, Miller PD, Delmas PD, et al. Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 2006; 21:1785.
  47. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996; 348:1535.
  48. McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 2001; 344:333.
  49. Nevitt MC, Chen P, Dore RK, et al. Reduced risk of back pain following teriparatide treatment: a meta-analysis. Osteoporos Int 2006; 17:273.
  50. Andreassen TT, Ejersted C, Oxlund H. Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 1999; 14:960.
  51. Huang TW, Chuang PY, Lin SJ, et al. Teriparatide Improves Fracture Healing and Early Functional Recovery in Treatment of Osteoporotic Intertrochanteric Fractures. Medicine (Baltimore) 2016; 95:e3626.
  52. Aspenberg P, Genant HK, Johansson T, et al. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 2010; 25:404.
  53. Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am 2011; 93:1583.
  54. Johansson T. PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures. A randomized, controlled study of 40 patients. Acta Orthop 2016; 87:79.
  55. Bhandari M, Jin L, See K, et al. Does Teriparatide Improve Femoral Neck Fracture Healing: Results From A Randomized Placebo-controlled Trial. Clin Orthop Relat Res 2016; 474:1234.
  56. Cosman F, Hattersley G, Hu MY, et al. Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors. J Bone Miner Res 2017; 32:17.
  57. McCloskey EV, Johansson H, Oden A, et al. The Effect of Abaloparatide-SC on Fracture Risk Is Independent of Baseline FRAX Fracture Probability: A Post Hoc Analysis of the ACTIVE Study. J Bone Miner Res 2017; 32:1625.
  58. Finkelstein JS, Leder BZ, Burnett SM, et al. Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men. J Clin Endocrinol Metab 2006; 91:2882.
  59. Walker MD, Cusano NE, Sliney J Jr, et al. Combination therapy with risedronate and teriparatide in male osteoporosis. Endocrine 2013; 44:237.
  60. Boonen S, Marin F, Obermayer-Pietsch B, et al. Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2008; 93:852.
  61. Miller PD, Delmas PD, Lindsay R, et al. Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J Clin Endocrinol Metab 2008; 93:3785.
  62. Obermayer-Pietsch BM, Marin F, McCloskey EV, et al. Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 2008; 23:1591.
  63. Cosman F, Wermers RA, Recknor C, et al. Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J Clin Endocrinol Metab 2009; 94:3772.
  64. Tsai JN, Uihlein AV, Lee H, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 2013; 382:50.
  65. Leder BZ, Tsai JN, Uihlein AV, et al. Two years of Denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial. J Clin Endocrinol Metab 2014; 99:1694.
  66. Ettinger B, San Martin J, Crans G, Pavo I. Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 2004; 19:745.
  67. Deal C, Omizo M, Schwartz EN, et al. Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res 2005; 20:1905.
  68. Cosman F, Nieves JW, Zion M, et al. Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy. Osteoporos Int 2008; 19:529.
  69. Cosman F, Nieves J, Woelfert L, et al. Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 2001; 16:925.
  70. Roe EB, Sanchez SD, Cann CE, et al. PTH-induced increases in bone density are preserved with estrogen: Results from a follow-up year in postmenopausal osteoporosis. J Bone Miner Res 2000; 15:S193.
  71. Ste-Marie LG, Schwartz SL, Hossain A, et al. Effect of teriparatide [rhPTH(1-34)] on BMD when given to postmenopausal women receiving hormone replacement therapy. J Bone Miner Res 2006; 21:283.
  72. Bashutski JD, Eber RM, Kinney JS, et al. Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 2010; 363:2396.