It has been over 2 years since parathyroid hormone (PTH 1–34) was approved in the US and Europe for the treatment of osteoporosis in postmenopausal women and men. Clinical experience with this peptide has enhanced confidence in its use and its application in specific clinical scenarios. There is no doubt that PTH 1–34 is safe and effective in reducing spine and non-vertebral fractures in men and women. However, the lack of several randomized placebo-controlled trials and their relatively short duration raise several questions that still need to be answered. This paper reviews three major areas of uncertainty: (1) Is there significant heterogeneity in the bone density response of individuals to PTH? If so, what factors are important predictors? (2) What other regimens are available for PTH use? (3) What, if anything, should the clinician do after PTH is discontinued? Answers to these questions will undoubtedly lead to even greater utilization of this drug and some of its future derivatives.

Neer R: FDA, Endocrinolic and Metabolic Advisory Committee Meetings, 7/2001.
Kanzawa M, Sugimoto T, Kanatani M, Chihara K: Involvement of osteoprotegerin/osteoclastogenesis inhibitory factor in the stimulation of osteoclast formation by parathyroid hormone in mouse bone cells. Eur J Endocrinol 2000;142:661–664.
Chiba S, Un-No M, Neer RM, Okada K, Serge GV, Lee K: Parathyroid hormone induces interleukin-6 gene expression in bone stromal cells of young rats. J Vet Med Sci 2002;64:641–644.
Lane NE, Kimmel DB, Nilsson MH, Cohen FE, Newton S, Nissenson RA, Strewler GJ: Bone-selective analogs of human PTH(1–34) increase bone formation in an ovariectomized rat model. J Bone Miner Res 1996;11:614–625.
Shen V, Dempster DW, Birchman R, Xu R, Lindsay R: Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol. J Clin Invest 1993;91:2479–2487.
Zeng G, Cole H, Smith S, Bryant H, Sato M: Bone effects in mice of ovariectomy and recombinant human PTH 1–34 are highly strain dependent. Bone 1998;23:448.
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH: Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434–1441.
Black D, Greenspan S, Ensrud K, Palermo L, McGowan J, Lang T, Garnero P, Bouxsein M, Bilezikian J, Rosen C: The effects of PTH and alendronate alone or in combination in post-menopausal osteoporosis. N Engl J Med 2003;349:1207–1215.
Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, Bilezikian JP: The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1–34)]. Osteoporos Int 2004;15:992–997.
Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, Gaich GA, Dalsky GP, Myers SL: Effects of teriparatide [recombinant human parathyroid hormone (1–34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 2003;18:539–543.
Rehman Q, Lang TF, Arnaud CD, Modin GW, Lane NE: Daily treatment with parathyroid hormone is associated with an increase in vertebral cross-sectional area in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 2003;14:77–81.
Finkelstein JS, Klibanski A, Arnold AL, Toth TL, Hornstein MD, Neer RM: Prevention of estrogen deficiency-related bone loss with human parathyroid hormone (1–34): A randomized controlled trial. J Am Med Assoc 1998;280:1067–1073.
Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, Shane E, Plavetic K, Muller R, Bilezikian J, Lindsay R: Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: A paired biopsy study. J Bone Miner Res 2001;16:1846–1853.
Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R: 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;88:1150–1156.
Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F: Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997;350:550–555.
Black D, Bilezikian J, Ensrud K, Greenspan S, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ: The effect of 1 year of alendronate following 1 year of PTH1–84: Two year results from the PTH and Alendronate (PaTH) Trial. N Engl J Med, in press.
Ettinger B, Ensrud KE, Wallace R, Johnson KC, Cummings SR, Yankov V, Vittinghoff E, Grady D: Effects of ultra low-dose transdermal estradiol on bone mineral density: A randomized clinical trial. Obstet Gynecol 2004;104:443–451.
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