A Fracture Does Not Adversely Affect Bone Mineral Density Responses after Teriparatide Treatment
Tóm tắt
Fracture leads to local and systemic catabolic physiologic changes. As teriparatide is an agent used to treat osteoporosis in patients with fragility fractures, it is unclear whether teriparatide treatment alters bone mineral density (BMD) and bone markers when given to patients with fractures. We asked whether BMD and bone marker responses would be blunted in patients with fractures placed on teriparatide after fracture compared with patients without fractures on teriparatide. We retrospectively collected data from 141 patients treated with teriparatide for osteoporosis. Seventy-seven patients received teriparatide after fractures (fracture group), whereas 64 were treated for other indications (nonfracture group). We determined BMD at the lumbar spine and at the proximal femur before and 12 and 24 months posttreatment. Bone markers (urine N-telopeptide [urine NTX], bone-specific alkaline phosphatase [BALP]) were measured at baseline and 3, 12, and 24 months posttreatment. Mean lumbar spine and hip BMDs at last followup increased from baseline with no differences between groups to approximately 9% and 4% at 24 months, respectively. Both bone markers increased from baseline in the nonfracture group, peaking at 12 months. For the fracture group, only urine NTX increased at 3 and 12 months posttreatment. Although the peak levels of both bone markers in the nonfracture group were greater, there was no difference between the two groups. Fracture does not have a negative effect on the BMD and bone marker responses to teriparatide treatment. Clinicians should anticipate comparable BMD responses when treating patients with teriparatide for osteoporotic fractures and for other indications. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Tài liệu tham khảo
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;14:960–968.
Andreassen TT, Fledelius C, Ejersted C, Oxlund H. Increases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone. Acta Orthop Scand. 2001;72:304–307.
Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, Garcia-Hernandez PA, Recknor CP, Einhorn TA, Dalsky GP, Mitlak BH, Fierlinger A, Lakshmanan MC. 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;25:404–414.
Bessette L, Jean S, Davison KS, Roy S, Ste-Marie LG, Brown JP. Factors influencing the treatment of osteoporosis following fragility fracture. Osteoporos Int. 2009;20:1911–1919.
Blumsohn A, Marin F, Nickelsen T, Brixen K, Sigurdsson G, Gonzalez de la Vera J, Boonen S, Liu-Leage S, Barker C, Eastell R; EUROFORS Study Group. Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide. Osteoporos Int. 2011;22:1935–1946.
Bonnick SL, Shulman L. Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both? Am J Med. 2006;119(4 suppl 1):S25–S31.
Boonen S, Singer AJ. Osteoporosis management: impact of fracture type on cost and quality of life in patients at risk for fracture I. Curr Med Res Opin. 2008;24:1781–1788.
Bouxsein ML, Chen P, Glass EV, Kallmes DF, Delmas PD, Mitlak BH. Teriparatide and raloxifene reduce the risk of new adjacent vertebral fractures in postmenopausal women with osteoporosis: results from two randomized controlled trials. J Bone Joint Surg Am. 2009;91:1329–1338.
Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. 1997;100:1475–1480.
Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, Krege JH. 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;94:3772–3780.
Cox G, Einhorn TA, Tzioupis C, Giannoudis PV. Bone-turnover markers in fracture healing. J Bone Joint Surg Br. 2010;92:329–334.
Delmas PD. Markers of bone turnover for monitoring treatment of osteoporosis with antiresorptive drugs. Osteoporos Int. 2000;11(suppl 6):S66–S76.
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.
Dijkman BG, Sprague S, Schemitsch EH, Bhandari M. When is a fracture healed? Radiographic and clinical criteria revisited. J Orthop Trauma. 2010;24(suppl 1):S76–S80.
Dobnig H, Turner RT. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology. 1995;136:3632–3638.
Eastell R, Nickelsen T, Marin F, Barker C, Hadji P, Farrerons J, Audran M, Boonen S, Brixen K, Gomes JM, Obermayer-Pietsch B, Avramidis A, Sigurdsson G, Gluer CC. Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European study of Forsteo (EUROFORS). J Bone Miner Res. 2009;24:726–736.
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;19:745–751.
Gehrig L, Lane J, O’Connor MI. Osteoporosis: management and treatment strategies for orthopaedic surgeons. J Bone Joint Surg Am. 2008;90:1362–1374.
Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, Kendler DL, McClung MR, Miller PD, Olszynski WP, Orwoll E, Yuen CK. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev. 2005;26:688–703.
Holzer G, Majeska RJ, Lundy MW, Hartke JR, Einhorn TA. Parathyroid hormone enhances fracture healing: a preliminary report. Clin Orthop Relat Res. 1999;366:258–263.
Ichimura S, Hasegawa M. [Biochemical markers of bone turnover: new aspect. Changes in bone turnover markers during fracture healing][in Japanese]. Clin Calcium. 2009;19:1102–1108.
Ivaska KK, Gerdhem P, Akesson K, Garnero P, Obrant KJ. Effect of fracture on bone turnover markers: a longitudinal study comparing marker levels before and after injury in 113 elderly women. J Bone Miner Res. 2007;22:1155–1164.
Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res. 2003;18:1932–1941.
Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest. 1999;104:439–446.
Joerring S, Jensen LT, Andersen GR, Johansen JS. Types I and III procollagen extension peptides in serum respond to fracture in humans. Arch Orthop Trauma Surg. 1992;111:265–267.
Larsson J, Lennmarken C, Martensson J, Sandstedt S, Vinnars E. Nitrogen requirements in severely injured patients. Br J Surg. 1990;77:413–416.
Larsson J, Liljedahl SO, Schildt B, Furst P, Vinnars E. Metabolic studies in multiple injured patients: clinical features, routine chemical analyses and nitrogen balance. Acta Chir Scand. 1981;147:317–324.
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.
McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005;165:1762–1768.
Miyauchi A, Matsumoto T, Shigeta H, Tsujimoto M, Thiebaud D, Nakamura T. Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study. J Bone Miner Metab. 2008;26:624–634.
Nakagawa H, Kamimura M, Takahara K, Hashidate H, Kawaguchi A, Uchiyama S, Miyasaka T. Changes in total alkaline phosphatase level after hip fracture: comparison between femoral neck and trochanter fractures. J Orthop Sci. 2006;11:135–139.
Nakajima A, Shimoji N, Shiomi K, Shimizu S, Moriya H, Einhorn TA, Yamazaki M. Mechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1–34). J Bone Miner Res. 2002;17:2038–2047.
Nakazawa T, Nakajima A, Shiomi K, Moriya H, Einhorn TA, Yamazaki M. Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1–34) on chondrogenesis in a model of experimental fracture healing. Bone. 2005;37:711–719.
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.
Nelson KM, Richards EW, Long CL, Martin KR, Geiger JW, Brooks SW, Gandy RE, Blakemore WS. Protein and energy balance following femoral neck fracture in geriatric patients. Metabolism. 1995;44:59–66.
Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, Audran M, Barker C, Anastasilakis AD, Fraser WD, Nickelsen T; EUROFORS Investigators. 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;23:1591–1600.
Onyia JE, Bidwell J, Herring J, Hulman J, Hock JM. In vivo, human parathyroid hormone fragment (hPTH 1–34) transiently stimulates immediate early response gene expression, but not proliferation, in trabecular bone cells of young rats. Bone. 1995;17:479–484.
Pape HC, Marcucio R, Humphrey C, Colnot C, Knobe M, Harvey EJ. Trauma-induced inflammation and fracture healing. J Orthop Trauma. 2010;24:522–525.
Patterson BM, Cornell CN, Carbone B, Levine B, Chapman D. Protein depletion and metabolic stress in elderly patients who have a fracture of the hip. J Bone Joint Surg Am. 1992;74:251–260.
Porter KH, Johnson MA. Dietary protein supplementation and recovery from femoral fracture. Nutr Rev. 1998;56:337–340.
Recker RR, Marin F, Ish-Shalom S, Moricke R, Hawkins F, Kapetanos G, de la Pena MP, Kekow J, Farrerons J, Sanz B, Oertel H, Stepan J. Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res. 2009;24:1358–1368.
Roux C, Garnero P, Thomas T, Sabatier JP, Orcel P, Audran M; Comite Scientifique du GRIO. Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis. Joint Bone Spine. 2005;72:26–31.
Rozental TD, Vazquez MA, Chacko AT, Ayogu N, Bouxsein ML. Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg Am. 2009;34:595–602.
Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128:801–809.
Seibel MJ. Biochemical markers of bone turnover: Part I. Biochemistry and variability. Clin Biochem Rev. 2005;26:97–122.
Skripitz R, Andreassen TT, Aspenberg P. Parathyroid hormone (1–34) increases the density of rat cancellous bone in a bone chamber: a dose-response study. J Bone Joint Surg Br. 2000;82:138–141.
Stein TP, Leskiw MJ, Wallace HW, Oram-Smith JC. Changes in protein synthesis after trauma: importance of nutrition. Am J Physiol. 1977;233:E348–E355.
Stoffel K, Engler H, Kuster M, Riesen W. Changes in biochemical markers after lower limb fractures. Clin Chem. 2007;53:131–134.
Veitch SW, Findlay SC, Hamer AJ, Blumsohn A, Eastell R, Ingle BM. Changes in bone mass and bone turnover following tibial shaft fracture. Osteoporos Int. 2006;17:364–372.
Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95:1555–1565.
Yang Q, Birkhahn RH. Metabolic rate and nitrogen balance after skeletal trauma in female and male rats. Nutrition. 1993;9:433–438.
Young Y, Fried LP, Kuo YH. Hip fractures among elderly women: longitudinal comparison of physiological function changes and health care utilization. J Am Med Dir Assoc. 2010;11:100–105.
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.