Skip to main content
Erschienen in: Calcified Tissue International 1/2015

01.07.2015 | Original Research

Effect of Combined Teriparatide and Monthly Risedronate Therapy on Cancellous Bone Mass in Orchidectomized Rats: A Bone Histomorphometry Study

verfasst von: Jun Iwamoto, Azusa Seki

Erschienen in: Calcified Tissue International | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

This study investigated the effects of combined teriparatide (an anabolic agent) and monthly risedronate (an anti-resorptive agent) therapy on cancellous bone mass in orchidectomized (ORX) rats. Fifty 14-week-old male Sprague–Dawley rats were randomized into five groups of ten animals each: sham-operation + vehicle; ORX + vehicle; ORX + risedronate (90 μg/kg subcutaneous, every 4 weeks); ORX + teriparatide (30 μg/kg subcutaneous, three times per week); and ORX + risedronate + teriparatide. After the 12-week experimental period, cancellous bone in the tibial proximal metaphysis was examined by static and dynamic histomorphometric analyses. ORX decreased bone volume per total volume (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Risedronate increased BV/TV and Tb.N above the sham control values, while teriparatide prevented the ORX-induced decrease in BV/TV and increased trabecular width (Tb.Wi) above sham control levels. Risedronate decreased Tb.Sp below control values, while teriparatide prevented the ORX-induced increase in Tb.Sp. The combination of teriparatide and risedronate further increased BV/TV and Tb.N and decreased Tb.Sp as a result of suppression of bone remodeling, compared with teriparatide alone. These results suggest that teriparatide and monthly risedronate exert different effects on cancellous bone structure and thus have additive effects on cancellous bone mass in ORX rats.
Literatur
1.
Zurück zum Zitat Mosekilde L, Vestergaar P, Rejnmark L (2013) The pathogenesis, treatment and prevention of osteoporosis in men. Drugs 73:15–29PubMedCrossRef Mosekilde L, Vestergaar P, Rejnmark L (2013) The pathogenesis, treatment and prevention of osteoporosis in men. Drugs 73:15–29PubMedCrossRef
2.
Zurück zum Zitat Murad MH, Drake MT, Mullan RJ, Mauck KF, Stuart LM, Lane MA, Abu Elnour NO, Erwin PJ, Hazem A, Puhan MA, Li T, Montori VM (2012) Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 97:1871–1880PubMedCrossRef Murad MH, Drake MT, Mullan RJ, Mauck KF, Stuart LM, Lane MA, Abu Elnour NO, Erwin PJ, Hazem A, Puhan MA, Li T, Montori VM (2012) Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 97:1871–1880PubMedCrossRef
3.
Zurück zum Zitat Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga M, Hagino H, Sone T, Yoshikawa H, Nishizawa Y, Fujita T, Shiraki M (2012) 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 97:3097–3106PubMedCrossRef Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga M, Hagino H, Sone T, Yoshikawa H, Nishizawa Y, Fujita T, Shiraki M (2012) 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 97:3097–3106PubMedCrossRef
4.
Zurück zum Zitat Cosman F, Eriksen EF, Recknor C, Miller PD, Guañabens N, Kasperk C, Papanastasiou P, Readie A, Rao H, Gasser JA, Bucci-Rechtweg C, Boonen S (2011) Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH (1–34)] in postmenopausal osteoporosis. J Bone Miner Res 26:503–511PubMedCrossRef Cosman F, Eriksen EF, Recknor C, Miller PD, Guañabens N, Kasperk C, Papanastasiou P, Readie A, Rao H, Gasser JA, Bucci-Rechtweg C, Boonen S (2011) Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH (1–34)] in postmenopausal osteoporosis. J Bone Miner Res 26:503–511PubMedCrossRef
5.
Zurück zum Zitat Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, Burnett-Bowie SA, Neer RM, Leder BZ (2013) Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 382:50–56PubMedCentralPubMedCrossRef Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, Burnett-Bowie SA, Neer RM, Leder BZ (2013) Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 382:50–56PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Walker MD, Cusano NE, Sliney J Jr, Romano M, Zhang C, McMahon DJ, Bilezikian JP (2013) Combination therapy with risedronate and teriparatide in male osteoporosis. Endocrine 44:237–246PubMedCrossRef Walker MD, Cusano NE, Sliney J Jr, Romano M, Zhang C, McMahon DJ, Bilezikian JP (2013) Combination therapy with risedronate and teriparatide in male osteoporosis. Endocrine 44:237–246PubMedCrossRef
7.
Zurück zum Zitat Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352PubMedCrossRef Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352PubMedCrossRef
8.
Zurück zum Zitat Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91PubMedCrossRef Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91PubMedCrossRef
9.
Zurück zum Zitat McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY, Hip Intervention Program Study Group (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333–340PubMedCrossRef McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY, Hip Intervention Program Study Group (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333–340PubMedCrossRef
10.
Zurück zum Zitat Harris ST, Watts NB, Li Z, Chines AA, Hanley DA, Brown JP (2004) Two-year efficacy and tolerability of risedronate once a week for the treatment of women with postmenopausal osteoporosis. Curr Med Res Opin 20:757–764PubMedCrossRef Harris ST, Watts NB, Li Z, Chines AA, Hanley DA, Brown JP (2004) Two-year efficacy and tolerability of risedronate once a week for the treatment of women with postmenopausal osteoporosis. Curr Med Res Opin 20:757–764PubMedCrossRef
11.
Zurück zum Zitat McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou CL, Man Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S, Delmas P (2013) Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data. Osteoporos Int 24:293–299PubMedCentralPubMedCrossRef McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou CL, Man Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S, Delmas P (2013) Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data. Osteoporos Int 24:293–299PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Ringe JD, Faber H, Farahmand P, Dorst A (2006) Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study. Rheumatol Int 26:427–431PubMedCrossRef Ringe JD, Faber H, Farahmand P, Dorst A (2006) Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study. Rheumatol Int 26:427–431PubMedCrossRef
13.
Zurück zum Zitat Confavreux CB, Canoui-Poitrine F, Schott AM, Ambrosi V, Tainturier V, Chapurlat RD (2012) Persistence at 1 year of oral antiosteoporotic drugs: a prospective study in a comprehensive health insurance database. Eur J Endocrinol 166:735–741PubMedCrossRef Confavreux CB, Canoui-Poitrine F, Schott AM, Ambrosi V, Tainturier V, Chapurlat RD (2012) Persistence at 1 year of oral antiosteoporotic drugs: a prospective study in a comprehensive health insurance database. Eur J Endocrinol 166:735–741PubMedCrossRef
14.
Zurück zum Zitat Iwamoto J, Takeda T, Katsumata T, Tanaka T, Ichimura S, Toyama Y (2002) Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats. Bone 30:360–367PubMedCrossRef Iwamoto J, Takeda T, Katsumata T, Tanaka T, Ichimura S, Toyama Y (2002) Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats. Bone 30:360–367PubMedCrossRef
15.
Zurück zum Zitat Iwamoto J, Yeh JK, Takeda T (2003) Effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats. J Bone Miner Res 18:776–783PubMedCrossRef Iwamoto J, Yeh JK, Takeda T (2003) Effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats. J Bone Miner Res 18:776–783PubMedCrossRef
16.
Zurück zum Zitat Iwamoto J, Takeda T, Yeh JK, Ichimura S, Toyama Y (2003) Effect of vitamin K2 on cortical and cancellous bones in orchidectomized young rats. Maturitas 44:19–27PubMedCrossRef Iwamoto J, Takeda T, Yeh JK, Ichimura S, Toyama Y (2003) Effect of vitamin K2 on cortical and cancellous bones in orchidectomized young rats. Maturitas 44:19–27PubMedCrossRef
17.
Zurück zum Zitat Iwamoto J, Takeda T, Ichimura S, Sato Y, Yeh JK (2003) Comparative effects of orchidectomy and sciatic neurectomy on cortical and cancellous bone in young growing rats. J Bone Miner Metab 21:211–216PubMed Iwamoto J, Takeda T, Ichimura S, Sato Y, Yeh JK (2003) Comparative effects of orchidectomy and sciatic neurectomy on cortical and cancellous bone in young growing rats. J Bone Miner Metab 21:211–216PubMed
18.
Zurück zum Zitat Iwamoto J, Takeda T, Ichimura S (2004) Differential effect of short-term etidronate treatment on three cancellous bone sites in orchidectomized adult rats. Keio J Med 53:12–17PubMedCrossRef Iwamoto J, Takeda T, Ichimura S (2004) Differential effect of short-term etidronate treatment on three cancellous bone sites in orchidectomized adult rats. Keio J Med 53:12–17PubMedCrossRef
19.
Zurück zum Zitat Iwamoto J, Takeda T, Matsumoto H, Sato Y, Yeh JK (2008) Beneficial effects of combined administration of alendronate and alfacalcidol on cancellous bone mass of the tibia in orchidectomized rats: a bone histomorphometry study. J Nutr Sci Vitaminol 54:11–17PubMedCrossRef Iwamoto J, Takeda T, Matsumoto H, Sato Y, Yeh JK (2008) Beneficial effects of combined administration of alendronate and alfacalcidol on cancellous bone mass of the tibia in orchidectomized rats: a bone histomorphometry study. J Nutr Sci Vitaminol 54:11–17PubMedCrossRef
20.
Zurück zum Zitat Shahnazari M, Yao W, Dai W, Wang B, Ionova-Martin SS, Ritchie RO, Heeren D, Burghardt AJ, Nicolella DP, Kimiecik MG, Lane NE (2010) Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats. Bone 46:1267–1274PubMedCentralPubMedCrossRef Shahnazari M, Yao W, Dai W, Wang B, Ionova-Martin SS, Ritchie RO, Heeren D, Burghardt AJ, Nicolella DP, Kimiecik MG, Lane NE (2010) Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats. Bone 46:1267–1274PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Iwamoto J, Seki A, Sato Y (2014) Effect of Intermittent administration of hPTH (1–34) on cortical bone geometry in rats treated with high-dose glucocorticoids. Chin J Physiol 57:231–237PubMedCrossRef Iwamoto J, Seki A, Sato Y (2014) Effect of Intermittent administration of hPTH (1–34) on cortical bone geometry in rats treated with high-dose glucocorticoids. Chin J Physiol 57:231–237PubMedCrossRef
22.
Zurück zum Zitat Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28:2–17PubMedCentralPubMedCrossRef Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28:2–17PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Turner RT, Hannon KS, Demers LM, Buchanan J, Bell NH (1989) Differential effects of gonadal function on bone histomorphometry in male and female rats. J Bone Miner Res 4:557–563PubMedCrossRef Turner RT, Hannon KS, Demers LM, Buchanan J, Bell NH (1989) Differential effects of gonadal function on bone histomorphometry in male and female rats. J Bone Miner Res 4:557–563PubMedCrossRef
25.
Zurück zum Zitat Gunness M, Orwoll E (1995) Early induction of alterations in cancellous and cortical bone histology after orchiectomy in mature rats. J Bone Miner Res 10:1735–1744PubMedCrossRef Gunness M, Orwoll E (1995) Early induction of alterations in cancellous and cortical bone histology after orchiectomy in mature rats. J Bone Miner Res 10:1735–1744PubMedCrossRef
26.
Zurück zum Zitat Yamaura M, Nakamura T, Tsurukami H, Hijioka A, Narusawa K, Ohnishi H, Ohta T, Hosoda K (1996) Local bone turnover in the metaphysis of the proximal tibia and the lumbar vertebra during the early periods after ovariectomy in rats. Calcif Tissue Int 58:52–59PubMedCrossRef Yamaura M, Nakamura T, Tsurukami H, Hijioka A, Narusawa K, Ohnishi H, Ohta T, Hosoda K (1996) Local bone turnover in the metaphysis of the proximal tibia and the lumbar vertebra during the early periods after ovariectomy in rats. Calcif Tissue Int 58:52–59PubMedCrossRef
27.
Zurück zum Zitat Díaz-Curiel M, de la Piedra C, Romero FI, Montero M, Gómez S, Lefort M, Carrascal MT, Phipps RJ (2008) Effect of risedronate on bone mass, remodelling and biomechanical strength in orchidectomized rats. Horm Res 70:93–99PubMedCrossRef Díaz-Curiel M, de la Piedra C, Romero FI, Montero M, Gómez S, Lefort M, Carrascal MT, Phipps RJ (2008) Effect of risedronate on bone mass, remodelling and biomechanical strength in orchidectomized rats. Horm Res 70:93–99PubMedCrossRef
28.
Zurück zum Zitat Khedr NF, El-Ashmawy NE, El-Bahrawy HA, Haggag AA, El-Abd EE (2013) Modulation of bone turnover in orchidectomized rats treated with raloxifene and risedronate. Fundam Clin Pharmacol 27:526–534PubMedCrossRef Khedr NF, El-Ashmawy NE, El-Bahrawy HA, Haggag AA, El-Abd EE (2013) Modulation of bone turnover in orchidectomized rats treated with raloxifene and risedronate. Fundam Clin Pharmacol 27:526–534PubMedCrossRef
29.
Zurück zum Zitat Montero M, Serfati D, Luna S, Díaz-Curiel M, Carrascal MT, Gomez S, De la Piedra C (2010) The effectiveness of intermittent rat parathyroid hormone (1–34) treatment on low bone mass due to oestrogen or androgen depletion in skeletally mature rats. Aging Male 13:59–73PubMedCrossRef Montero M, Serfati D, Luna S, Díaz-Curiel M, Carrascal MT, Gomez S, De la Piedra C (2010) The effectiveness of intermittent rat parathyroid hormone (1–34) treatment on low bone mass due to oestrogen or androgen depletion in skeletally mature rats. Aging Male 13:59–73PubMedCrossRef
30.
Zurück zum Zitat Gabet Y, Kohavi D, Müller R, Chorev M, Bab I (2005) Intermittently administered parathyroid hormone 1–34 reverses bone loss and structural impairment in orchidectomized adult rats. Osteoporos Int 16:1436–1443PubMedCrossRef Gabet Y, Kohavi D, Müller R, Chorev M, Bab I (2005) Intermittently administered parathyroid hormone 1–34 reverses bone loss and structural impairment in orchidectomized adult rats. Osteoporos Int 16:1436–1443PubMedCrossRef
31.
Zurück zum Zitat Compston JE (2007) Skeletal actions of intermittent parathyroid hormone: effects on bone remodelling and structure. Bone 40:1447–1452PubMedCrossRef Compston JE (2007) Skeletal actions of intermittent parathyroid hormone: effects on bone remodelling and structure. Bone 40:1447–1452PubMedCrossRef
32.
Zurück zum Zitat Iwamoto J, Seki A, Sato Y (2014) Effect of combined teriparatide and monthly minodronic acid therapy on cancellous bone mass in ovariectomized rats: a bone histomorphometry study. Bone 64:88–94PubMedCrossRef Iwamoto J, Seki A, Sato Y (2014) Effect of combined teriparatide and monthly minodronic acid therapy on cancellous bone mass in ovariectomized rats: a bone histomorphometry study. Bone 64:88–94PubMedCrossRef
Metadaten
Titel
Effect of Combined Teriparatide and Monthly Risedronate Therapy on Cancellous Bone Mass in Orchidectomized Rats: A Bone Histomorphometry Study
verfasst von
Jun Iwamoto
Azusa Seki
Publikationsdatum
01.07.2015
Verlag
Springer US
Erschienen in
Calcified Tissue International / Ausgabe 1/2015
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-015-0006-5

Weitere Artikel der Ausgabe 1/2015

Calcified Tissue International 1/2015 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.