Parathyroid Hormone (1–34) Transiently Protects Against Radiation-Induced Bone Fragility
Tóm tắt
Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1–34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility.
Tài liệu tham khảo
Baxter NN, Habermann EB, Tepper JE, Durham SB, Virnig BA (2005) Risk of pelvic fractures in older women following pelvic irradiation. JAMA 294:2587–2593
Oh D, Huh SJ, Nam H, Park W, Han Y, do Lim H, Ahn YC, Lee JW, Kim BG, Bae DS, Lee JH (2008) Pelvic insufficiency fracture after pelvic radiotherapy for cervical cancer: analysis of risk factors. Int J Radiat Oncol Biol Phys 70:1183–1188
Voroney JP, Hope A, Dahele MR, Purdie TG, Franks KN, Pearson S, Cho JB, Sun A, Payne DG, Bissonnette JP, Bezjak A, Brade AM (2009) Chest wall pain and rib fracture after stereotactic radiotherapy for peripheral non-small cell lung cancer. J Thorac Oncol 4:1035–1037
Park SH, Kim JC, Lee JE, Park IK (2011) Pelvic insufficiency fracture after radiotherapy in patients with cervical cancer in the era of PET/CT. Radiat Oncol J 29:269–276
Dunlap NE, Cai J, Biedermann GB, Yang W, Benedict SH, Sheng K, Schefter TE, Kavanagh BD, Larner JM (2010) Chest wall volume receiving >30 Gy predicts risk of severe pain and/or rib fracture after lung stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 76:796–801
Helmstedter CS, Goebel M, Zlotecki R, Scarborough MT (2001) Pathologic fractures after surgery and radiation for soft tissue tumors. Clin Orthop Relat Res 389:165–172
Holt GE, Griffin AM, Pintilie M, Wunder JS, Catton C, O’Sullivan B, Bell RS (2005) Fractures following radiotherapy and limb-salvage surgery for lower extremity soft-tissue sarcomas. A comparison of high-dose and low-dose radiotherapy. J Bone Joint Surg Am 87:315–319
Bandstra ER, Pecaut MJ, Anderson ER, Willey JS, De Carlo F, Stock SR, Gridley DS, Nelson GA, Levine HG, Bateman TA (2008) Long-term dose response of trabecular bone in mice to proton radiation. Radiat Res 169:607–614
Hamilton SA, Pecaut MJ, Gridley DS, Travis ND, Bandstra ER, Willey JS, Nelson GA, Bateman TA (2006) A murine model for bone loss from therapeutic and space-relevant sources of radiation. J Appl Physiol 101:789–793
Willey JS, Livingston EW, Robbins ME, Bourland JD, Tirado-Lee L, Smith-Sielicki H, Bateman TA (2010) Risedronate prevents early radiation-induced osteoporosis in mice at multiple skeletal locations. Bone 46:101–111
Willey JS, Lloyd SA, Robbins ME, Bourland JD, Smith-Sielicki H, Bowman LC, Norrdin RW, Bateman TA (2008) Early increase in osteoclast number in mice after whole-body irradiation with 2 Gy X rays. Radiat Res 170:388–392
Guise TA (2006) Bone loss and fracture risk associated with cancer therapy. Oncologist 11:1121–1131
Oest ME, Franken V, Kuchera T, Strauss J, Damron TA (2014) Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation. J Orthop Res 33:334–342
Oteo-Alvaro A, Moreno E (2010) Atrophic humeral shaft nonunion treated with teriparatide (rh PTH 1-34): a case report. J Shoulder Elbow Surg 19:22–28
Paridis D, Karachalios T (2011) Atrophic femoral bone nonunion treated with 1-84 PTH. J Musculoskelet Neuronal Interact 11:320–322 quiz 323
Subbiah V, Madsen VS, Raymond AK, Benjamin RS, Ludwig JA (2010) Of mice and men: divergent risks of teriparatide-induced osteosarcoma. Osteoporos Int 21:1041–1045
Gong B, Oest ME, Mann KA, Damron TA, Morris MD (2013) Raman spectroscopy demonstrates prolonged alteration of bone chemical composition following extremity localized irradiation. Bone 57:252–258
Oest ME, Damron TA (2014) Focal therapeutic irradiation induces an early transient increase in bone glycation. Radiat Res 181:439–443
Fowler JF (2010) 21 years of biologically effective dose. Br J Radiol 83:554–568
Hopewell JW (2003) Radiation-therapy effects on bone density. Med Pediatr Oncol 41:208–211
Doube M, Klosowski MM, Arganda-Carreras I, Cordelieres FP, Dougherty RP, Jackson JS, Schmid B, Hutchinson JR, Shefelbine SJ (2010) BoneJ: free and extensible bone image analysis in ImageJ. Bone 47:1076–1079
Wernle JD, Damron TA, Allen MJ, Mann KA (2010) Local irradiation alters bone morphology and increases bone fragility in a mouse model. J Biomech 43:2738–2746
van der Meulen MC, Jepsen KJ, Mikic B (2001) Understanding bone strength: size isn’t everything. Bone 29:101–104
Jepsen K (2011) Functional interactions among morphologic and tissue quality traits define bone quality. Clin Orthop Relat Res 469:2150–2159
Li X, Qin L, Bergenstock M, Bevelock LM, Novack DV, Partridge NC (2007) Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. J Biol Chem 282:33098–33106
Whitfield JF (2005) Parathyroid hormone (PTH) and hematopoiesis: new support for some old observations. J Cell Biochem 96:278–284
Whitfield JF (2006) Parathyroid hormone: a novel tool for treating bone marrow depletion in cancer patients caused by chemotherapeutic drugs and ionizing radiation. Cancer Lett 244:8–15
Jacome-Galarza CE, Lee SK, Lorenzo JA, Aguila HL (2011) Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow. J Bone Miner Res 26:1207–1216
Jilka RL (2013) The relevance of mouse models for investigating age-related bone loss in humans. J Gerotol A Biol Sci Med Sci 68:1209–1217
Arrington SA, Fisher ER, Willick GE, Mann KA, Allen MJ (2010) Anabolic and antiresorptive drugs improve trabecular microarchitecture and reduce fracture risk following radiation therapy. Calcif Tissue Int 87:263–272
Deshpande SS, Gallagher KK, Donneys A, Tchanque-Fossuo CN, Sarhaddi D, Nelson NS, Chepeha DB, Buchman SR (2013) Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis. Plast Reconstr Surg 132:91e–100e
Gallagher KK, Deshpande S, Tchanque-Fossuo CN, Donneys A, Sarhaddi D, Nelson NS, Chepeha DB, Buchman SR (2013) Role of parathyroid hormone therapy in reversing radiation-induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis. Head Neck 35:1732–1737
Chandra A, Lan S, Zhu J, Lin T, Zhang X, Siclari VA, Altman AR, Cengel KA, Liu XS, Qin L (2013) PTH prevents the adverse effects of focal radiation on bone architecture in young rats. Bone 55:449–457
Chandra A, Lin T, Tribble MB, Zhu J, Altman AR, Tseng WJ, Zhang Y, Akintoye SO, Cengel K, Liu XS, Qin L (2014) PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival. Bone 67:33–40
Koh AJ, Novince CM, Li X, Wang T, Taichman RS, McCauley LK (2011) An irradiation-altered bone marrow microenvironment impacts anabolic actions of PTH. Endocrinology 152:4525–4536
Acil Y, Springer IN, Niehoff P, Gassling V, Warnke PH, Acmaz S, Sonmez TT, Kimmig B, Lefteris V, Wiltfang J (2007) Proof of direct radiogenic destruction of collagen in vitro. Strahlenther Onkol 183:374–379
Green DE, Adler BJ, Chan ME, Lennon JJ, Acerbo AS, Miller LM, Rubin CT (2013) Altered composition of bone as triggered by irradiation facilitates the rapid erosion of the matrix by both cellular and physicochemical processes. PLoS One 8:e64952
Cao X, Wu X, Frassica D, Yu B, Pang L, Xian L, Wan M, Lei W, Armour M, Tryggestad E, Wong J, Wen CY, Lu WW, Frassica FJ (2011) Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells. Proc Natl Acad Sci USA 108:1609–1614
Green DE, Rubin CT (2014) Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors. Bone 63C:87–94
Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ (2009) Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460:259–263
Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846
Calvi LM, Bromberg O, Rhee Y, Weber JM, Smith JN, Basil MJ, Frisch BJ, Bellido T (2012) Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. Blood 119:2489–2499
Charles JF, Aliprantis AO (2014) Osteoclasts: more than ‘bone eaters’. Trends Mol Med 20:449–459
Huber BC, Grabmaier U, Brunner S (2014) Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration. World J Stem Cells 6:637–643
Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561