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Erschienen in:

01.07.2010

Parathyroid Hormone and Bone Healing

Erschienen in: Calcified Tissue International | Ausgabe 1/2010

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Abstract

Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

Gaston MS, Simpson AH (2007) Inhibition of fracture healing. J Bone Joint Surg Br 89:1553–1560PubMed

Hayda RA, Brighton CT, Esterhai JL Jr (1998) Pathophysiology of delayed healing. Clin Orthop Relat Res 355(Suppl):S31–S40CrossRefPubMed

Axelrad TW, Kakar S, Einhorn TA (2007) New technologies for the enhancement of skeletal repair. Injury 38(Suppl 1):S49–S62PubMed

Quattrocchi E, Kourlas H (2004) Teriparatide: a review. Clin Ther 26:841–854CrossRefPubMed

Wronski TJ, Yen CF, Qi H, Dann LM (1993) Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats. Endocrinology 132:823–831CrossRefPubMed

Sato M, Zeng GQ, Turner CH (1997) Biosynthetic human parathyroid hormone (1–34) effects on bone quality in aged ovariectomized rats. Endocrinology 138:4330–4337CrossRefPubMed

Jerome CP, Burr DB, Van Bibber T, Hock JM, Brommage R (2001) 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 28:150–159CrossRefPubMed

Sato M, Westmore M, Ma YL, Schmidt A, Zeng QQ, Glass EV, Vahle J, Brommage R, Jerome CP, Turner CH (2004) Teriparatide [PTH(1–34)] strengthens the proximal femur of ovariectomized nonhuman primates despite increasing porosity. J Bone Miner Res 19:623–629CrossRefPubMed

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 (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441CrossRefPubMed

10.

Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, Blosch CM, Mathisen AL, Morris SA, Marriott TB (2007) 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 146:326–339PubMed

11.

Andreassen TT, Ejersted C, Oxlund H (1999) Intermittent parathyroid hormone (1–34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 14:960–968CrossRefPubMed

12.

Andreassen TT, Willick GE, Morley P, Whitfield JF (2004) Treatment with parathyroid hormone hPTH(1–34), hPTH(1–31), and monocyclic hPTH(1–31) enhances fracture strength and callus amount after withdrawal fracture strength and callus mechanical quality continue to increase. Calcif Tissue Int 74:351–356CrossRefPubMed

13.

Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, Einhorn TA (2005) Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1–34). J Bone Joint Surg Am 87:731–741CrossRefPubMed

14.

Holzer G, Majeska RJ, Lundy MW, Hartke JR, Einhorn TA (1999) Parathyroid hormone enhances fracture healing. A preliminary report. Clin Orthop Relat Res 366:258–263CrossRefPubMed

15.

Komatsubara S, Mori S, Mashiba T, Nonaka K, Seki A, Akiyama T, Miyamoto K, Cao Y, Manabe T, Norimatsu H (2005) Human parathyroid hormone (1–34) accelerates the fracture healing process of woven to lamellar bone replacement and new cortical shell formation in rat femora. Bone 36:678–687CrossRefPubMed

16.

Manabe T, Mori S, Mashiba T, Kaji Y, Iwata K, Komatsubara S, Seki A, Sun YX, Yamamoto T (2007) Human parathyroid hormone (1–34) accelerates natural fracture healing process in the femoral osteotomy model of cynomolgus monkeys. Bone 40:1475–1482CrossRefPubMed

17.

Jee WS, Yao W (2001) Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 1:193–207PubMed

18.

Tsiridis E, Morgan EF, Bancroft JM, Song M, Kain M, Gerstenfeld L, Einhorn TA, Bouxsein ML, Tornetta P III (2007) Effects of OP-1 and PTH in a new experimental model for the study of metaphyseal bone healing. J Orthop Res 25:1193–1203CrossRefPubMed

19.

Morgan EF, Mason ZD, Bishop G, Davis AD, Wigner NA, Gerstenfeld LC, Einhorn TA (2008) Combined effects of recombinant human BMP-7 (rhBMP-7) and parathyroid hormone (1–34) in metaphyseal bone healing. Bone 43:1031–1038CrossRefPubMed

20.

Rozen N, Lewinson D, Bick T, Jacob ZC, Stein H, Soudry M (2007) Fracture repair: modulation of fracture-callus and mechanical properties by sequential application of IL-6 following PTH 1–34 or PTH 28–48. Bone 41:437–445CrossRefPubMed

21.

Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger JO (2006) Fracture healing in the elderly patient. Exp Gerontol 41:1080–1093CrossRefPubMed

22.

Andreassen TT, Fledelius C, Ejersted C, Oxlund H (2001) Increases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone. Acta Orthop Scand 72:304–307CrossRefPubMed

23.

Yingjie H, Ge Z, Yisheng W, Ling Q, Hung WY, Kwoksui L, Fuxing P (2007) Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats. Bone 41:631–638CrossRefPubMed

24.

McCann RM, Colleary G, Geddis C, Clarke SA, Jordan GR, Dickson GR, Marsh D (2008) Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model. J Orthop Res 26:384–393CrossRefPubMed

25.

Walsh WR, Sherman P, Howlett CR, Sonnabend DH, Ehrlich MG (1997) Fracture healing in a rat osteopenia model. Clin Orthop Relat Res 342:218–227CrossRefPubMed

26.

Namkung-Matthai H, Appleyard R, Jansen J, Hao LJ, Maastricht S, Swain M, Mason RS, Murrell GA, Diwan AD, Diamond T (2001) Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone 28:80–86CrossRefPubMed

27.

Jahng JS, Kim HW (2000) Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. Orthopedics 23:1089–1094PubMed

28.

Nozaka K, Miyakoshi N, Kasukawa Y, Maekawa S, Noguchi H, Shimada Y (2008) Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats. Bone 42:90–97CrossRefPubMed

29.

Gabet Y, Muller R, Levy J, Dimarchi R, Chorev M, Bab I, Kohavi D (2006) Parathyroid hormone 1–34 enhances titanium implant anchorage in low-density trabecular bone: a correlative micro-computed tomographic and biomechanical analysis. Bone 39:276–282CrossRefPubMed

30.

Shirota T, Tashiro M, Ohno K, Yamaguchi A (2003) Effect of intermittent parathyroid hormone (1–34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats. J Oral Maxillofac Surg 61:471–480CrossRefPubMed

31.

Dayer R, Rizzoli R, Kaelin A, Ammann P (2006) Low protein intake is associated with impaired titanium implant osseointegration. J Bone Miner Res 21:258–264CrossRefPubMed

32.

Dayer R, Badoud I, Rizzoli R, Ammann P (2007) Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate. J Bone Miner Res 22:1526–1533CrossRefPubMed

33.

Skripitz R, Andreassen TT, Aspenberg P (2000) Strong effect of PTH (1–34) on regenerating bone: a time sequence study in rats. Acta Orthop Scand 71:619–624CrossRefPubMed

34.

Skripitz R, Andreassen TT, Aspenberg P (2000) Parathyroid hormone (1–34) increases the density of rat cancellous bone in a bone chamber. A dose-response study. J Bone Joint Surg Br 82:138–141CrossRefPubMed

35.

Skripitz R, Aspenberg P (2001) Implant fixation enhanced by intermittent treatment with parathyroid hormone. J Bone Joint Surg Br 83:437–440CrossRefPubMed

36.

Skripitz R, Aspenberg P (2001) Early effect of parathyroid hormone (1–34) on implant fixation. Clin Orthop Relat Res 392:427–432CrossRefPubMed

37.

Aspenberg P, Wermelin K, Tengwall P, Fahlgren A (2008) Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats. Acta Orthop 79:111–115CrossRefPubMed

38.

Skripitz R, Aspenberg P (2001) Parathyroid hormone (1–34) increases attachment of PMMA cement to bone. J Orthop Sci 6:540–544CrossRefPubMed

39.

Pettway GJ, Schneider A, Koh AJ, Widjaja E, Morris MD, Meganck JA, Goldstein SA, McCauley LK (2005) Anabolic actions of PTH (1–34): use of a novel tissue engineering model to investigate temporal effects on bone. Bone 36:959–970CrossRefPubMed

40.

Iwaniec UT, Trevisiol CH, Maddalozzo GF, Rosen CJ, Turner RT (2008) Effects of low-dose parathyroid hormone on bone mass, turnover, and ectopic osteoinduction in a rat model for chronic alcohol abuse. Bone 42:695–701CrossRefPubMed

41.

Nakajima A, Shimoji N, Shiomi K, Shimizu S, Moriya H, Einhorn TA, Yamazaki M (2002) Mechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1–34). J Bone Miner Res 17:2038–2047CrossRefPubMed

42.

Lawrence JP, Ennis F, White AP, Magit D, Polzhofer G, Drespe I, Troiano NW, Grauer JN (2006) Effect of daily parathyroid hormone (1–34) on lumbar fusion in a rat model. Spine J 6:385–390CrossRefPubMed

43.

Abe Y, Takahata M, Ito M, Irie K, Abumi K, Minami A (2007) Enhancement of graft bone healing by intermittent administration of human parathyroid hormone (1–34) in a rat spinal arthrodesis model. Bone 41:775–785CrossRefPubMed

44.

O’Loughlin PF, Cunningham ME, Bukata SV, Tomin E, Poynton AR, Doty SB, Sama AA, Lane JM (2009) Parathyroid hormone (1–34) augments spinal fusion, fusion mass volume, and fusion mass quality in a rabbit spinal fusion model. Spine 34:121–130CrossRefPubMed

45.

Seebach C, Skripitz R, Andreassen TT, Aspenberg P (2004) Intermittent parathyroid hormone (1–34) enhances mechanical strength and density of new bone after distraction osteogenesis in rats. J Orthop Res 22:472–478CrossRefPubMed

46.

Hashimoto T, Shigetomi M, Ohno T, Matsunaga T, Muramatsu K, Tanaka H, Sugiyama T, Taguchi T (2007) Sequential treatment with intermittent low-dose human parathyroid hormone (1–34) and bisphosphonate enhances large-size skeletal reconstruction by vascularized bone transplantation. Calcif Tissue Int 81:232–239CrossRefPubMed

47.

Jung RE, Hammerle CH, Kokovic V, Weber FE (2007) Bone regeneration using a synthetic matrix containing a parathyroid hormone peptide combined with a grafting material. Int J Oral Maxillofac Implants 22:258–266PubMed

48.

Jung RE, Cochran DL, Domken O, Seibl R, Jones AA, Buser D, Hammerle CH (2007) The effect of matrix bound parathyroid hormone on bone regeneration. Clin Oral Implants Res 18:319–325CrossRefPubMed

49.

Andreassen TT, Cacciafesta V (2004) Intermittent parathyroid hormone treatment enhances guided bone regeneration in rat calvarial bone defects. J Craniofac Surg 15:424–427CrossRefPubMed

50.

Di Bisceglie L, Fata G, Di Molfetta V (2007) Teriparatide use to accelerate fracture repair in delayed healing of complex fractures in military personel: a clinical case. In: Presented at the 34th European symposium on calcified tissue, Copenhagen, 5–9 May 2009, Poster-number P048-M

51.

Resmini G, Iolascon G (2007) 79-year-old post-menopausal woman with humerus fracture during teriparatide treatment. Aging Clin Exp Res 19:30–31PubMed

52.

Yu CT, Wu JK, Chang CC, Chen CL, Wei JC (2008) Early callus formation in human hip fracture treated with internal fixation and teriparatide. J Rheumatol 35:2082–2083PubMed

53.

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 (2009) 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. doi:10.1359/jbmr.090731

54.

Komatsu DE, Brune KA, Liu H, Schmidt AL, Han B, Zeng QQ, Yang X, Nunes JS, Lu Y, Geiser AG, Ma YL, Wolos JA, Westmore MS, Sato M (2009) Longitudinal in vivo analysis of the region-specific efficacy of parathyroid hormone in a rat cortical defect model. Endocrinology 150:1570–1579CrossRefPubMed

55.

Nakazawa T, Nakajima A, Shiomi K, Moriya H, Einhorn TA, Yamazaki M (2005) Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1–34) on chondrogenesis in a model of experimental fracture healing. Bone 37:711–719CrossRefPubMed

56.

Okazaki K, Jingushi S, Ikenoue T, Urabe K, Sakai H, Iwamoto Y (2003) Expression of parathyroid hormone-related peptide and insulin-like growth factor I during rat fracture healing. J Orthop Res 21:511–520CrossRefPubMed

57.

Kakar S, Einhorn TA, Vora S, Miara LJ, Hon G, Wigner NA, Toben D, Jacobsen KA, Al-Sebaei MO, Song M, Trackman PC, Morgan EF, Gerstenfeld LC, Barnes GL (2007) Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures. J Bone Miner Res 22:1903–1912CrossRefPubMed

58.

Kaback LA, Soung DY, Naik A, Geneau G, Schwarz EM, Rosier RN, O’Keefe RJ, Drissi H (2008) Teriparatide (1–34 human PTH) regulation of osterix during fracture repair. J Cell Biochem 105:219–226CrossRefPubMed

59.

Goldhahn J, Scheele WH, Mitlak BH, Abadie E, Aspenberg P, Augat P, Brandi ML, Burlet N, Chines A, Delmas PD, Dupin-Roger I, Ethgen D, Hanson B, Hartl F, Kanis JA, Kewalramani R, Laslop A, Marsh D, Ormarsdottir S, Rizzoli R, Santora A, Schmidmaier G, Wagener M, Reginster JY (2008) Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis. Bone 43:343–347CrossRefPubMed

Titel: Parathyroid Hormone and Bone Healing
Publikationsdatum: 01.07.2010
Erschienen in: Calcified Tissue International / Ausgabe 1/2010
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-010-9360-5

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