Skip to main content
Erschienen in: Endocrine 1/2018

13.10.2017 | Meta-Analysis

Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis

verfasst von: Maya Barake, Asma Arabi, Nancy Nakhoul, Ghada El-Hajj Fuleihan, Sarah El Ghandour, Anne Klibanski, Nicholas A. Tritos

Erschienen in: Endocrine | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear.

Methods

We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible.

Results

We included eight studies. Seven randomized 272 post-menopausal women, 61–69 years, to GH or control, for 6–24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = −0.01 [−0.04, 0.02]), total hip (WMD = 0 [−0.05, 0.06]) or femoral neck (WMD = 0 [−0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention.

Conclusion

GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.
Literatur
3.
Zurück zum Zitat P.V. Carroll, E.R. Christ, B.A. Bengtsson, L. Carlsson, J.S. Christiansen, D. Clemmons, R. Hintz, K. Ho, Z. Laron, P. Sizonenko, P.H. Sonksen, T. Tanaka, M. Thorne, Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J. Clin. Endocrinol. Metab. 83(2), 382–395 (1998). https://doi.org/10.1210/jcem.83.2.4594 CrossRefPubMed P.V. Carroll, E.R. Christ, B.A. Bengtsson, L. Carlsson, J.S. Christiansen, D. Clemmons, R. Hintz, K. Ho, Z. Laron, P. Sizonenko, P.H. Sonksen, T. Tanaka, M. Thorne, Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J. Clin. Endocrinol. Metab. 83(2), 382–395 (1998). https://​doi.​org/​10.​1210/​jcem.​83.​2.​4594 CrossRefPubMed
4.
Zurück zum Zitat G. Mazziotti, A. Bianchi, S. Bonadonna, M. Nuzzo, V. Cimino, A. Fusco, L. De Marinis, A. Giustina, Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy. J. Bone Miner. Res. 21(4), 520–528 (2006). https://doi.org/10.1359/jbmr.060112 CrossRefPubMed G. Mazziotti, A. Bianchi, S. Bonadonna, M. Nuzzo, V. Cimino, A. Fusco, L. De Marinis, A. Giustina, Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy. J. Bone Miner. Res. 21(4), 520–528 (2006). https://​doi.​org/​10.​1359/​jbmr.​060112 CrossRefPubMed
6.
Zurück zum Zitat T. Rosen, L. Wilhelmsen, K. Landin-Wilhelmsen, G. Lappas, B.A. Bengtsson, Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur. J. Endocrinol. 137(3), 240–245 (1997)CrossRefPubMed T. Rosen, L. Wilhelmsen, K. Landin-Wilhelmsen, G. Lappas, B.A. Bengtsson, Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur. J. Endocrinol. 137(3), 240–245 (1997)CrossRefPubMed
7.
Zurück zum Zitat C. Wuster, R. Abs, B.A. Bengtsson, H. Bennmarker, U. Feldt-Rasmussen, E. Hernberg-Stahl, J.P. Monson, B. Westberg, P. Wilton, K.S. Group, K.I.B.P. the; Upjohn International Metabolic, D., The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J. Bone Miner. Res. 16(2), 398–405 (2001). https://doi.org/10.1359/jbmr.2001.16.2.398 CrossRefPubMed C. Wuster, R. Abs, B.A. Bengtsson, H. Bennmarker, U. Feldt-Rasmussen, E. Hernberg-Stahl, J.P. Monson, B. Westberg, P. Wilton, K.S. Group, K.I.B.P. the; Upjohn International Metabolic, D., The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J. Bone Miner. Res. 16(2), 398–405 (2001). https://​doi.​org/​10.​1359/​jbmr.​2001.​16.​2.​398 CrossRefPubMed
9.
Zurück zum Zitat D.R. Clemmons, J.J. Van Wyk, Factors controlling blood concentration of somatomedin C. Clin. Endocrinol. Metab. 13(1), 113–143 (1984)CrossRefPubMed D.R. Clemmons, J.J. Van Wyk, Factors controlling blood concentration of somatomedin C. Clin. Endocrinol. Metab. 13(1), 113–143 (1984)CrossRefPubMed
10.
Zurück zum Zitat A. Iranmanesh, G. Lizarralde, J.D. Veldhuis, Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J. Clin. Endocrinol. Metab. 73(5), 1081–1088 (1991). https://doi.org/10.1210/jcem-73-5-1081 CrossRefPubMed A. Iranmanesh, G. Lizarralde, J.D. Veldhuis, Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J. Clin. Endocrinol. Metab. 73(5), 1081–1088 (1991). https://​doi.​org/​10.​1210/​jcem-73-5-1081 CrossRefPubMed
12.
Zurück zum Zitat S. Ljunghall, A.G. Johansson, P. Burman, O. Kampe, E. Lindh, F.A. Karlsson, Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J. Intern. Med. 232(1), 59–64 (1992)CrossRefPubMed S. Ljunghall, A.G. Johansson, P. Burman, O. Kampe, E. Lindh, F.A. Karlsson, Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J. Intern. Med. 232(1), 59–64 (1992)CrossRefPubMed
13.
Zurück zum Zitat M. Munoz-Torres, P. Mezquita-Raya, F. Lopez-Rodriguez, E. Torres-Vela, J. de Dios Luna, F. Escobar-Jimenez, The contribution of IGF-I to skeletal integrity in postmenopausal women. Clin. Endocrinol. 55(6), 759–766 (2001)CrossRef M. Munoz-Torres, P. Mezquita-Raya, F. Lopez-Rodriguez, E. Torres-Vela, J. de Dios Luna, F. Escobar-Jimenez, The contribution of IGF-I to skeletal integrity in postmenopausal women. Clin. Endocrinol. 55(6), 759–766 (2001)CrossRef
14.
Zurück zum Zitat P. Garnero, E. Sornay-Rendu, P.D. Delmas, Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet 355(9207), 898–899 (2000)CrossRefPubMed P. Garnero, E. Sornay-Rendu, P.D. Delmas, Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet 355(9207), 898–899 (2000)CrossRefPubMed
17.
Zurück zum Zitat M. Saaf, A. Hilding, M. Thoren, S. Troell, K. Hall, Growth hormone treatment of osteoporotic postmenopausal women - a one-year placebo-controlled study. Eur. J. Endocrinol. 140(5), 390–399 (1999)CrossRefPubMed M. Saaf, A. Hilding, M. Thoren, S. Troell, K. Hall, Growth hormone treatment of osteoporotic postmenopausal women - a one-year placebo-controlled study. Eur. J. Endocrinol. 140(5), 390–399 (1999)CrossRefPubMed
19.
Zurück zum Zitat H. Liu, D.M. Bravata, I. Olkin, S. Nayak, B. Roberts, A.M. Garber, A.R. Hoffman, Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann. Intern. Med. 146(2), 104–115 (2007)CrossRefPubMed H. Liu, D.M. Bravata, I. Olkin, S. Nayak, B. Roberts, A.M. Garber, A.R. Hoffman, Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann. Intern. Med. 146(2), 104–115 (2007)CrossRefPubMed
21.
Zurück zum Zitat A. Cranney, P. Tugwell, S. Cummings, P. Sambrook, J. Adachi, A.J. Silman, W.J. Gillespie, D.T. Felson, B. Shea, G. Wells, Osteoporosis clinical trials endpoints: candidate variables and clinimetric properties. J. Rheumatol. 24(6), 1222–1229 (1997)PubMed A. Cranney, P. Tugwell, S. Cummings, P. Sambrook, J. Adachi, A.J. Silman, W.J. Gillespie, D.T. Felson, B. Shea, G. Wells, Osteoporosis clinical trials endpoints: candidate variables and clinimetric properties. J. Rheumatol. 24(6), 1222–1229 (1997)PubMed
23.
Zurück zum Zitat R.J. Erdtsieck, H.A. Pols, N.K. Valk, B.M. van Ouwerkerk, S.W. Lamberts, P. Mulder, J.C. Birkenhager, Treatment of post-menopausal osteoporosis with a combination of growth hormone and pamidronate: a placebo controlled trial. Clin. Endocrinol. 43(5), 557–565 (1995)CrossRef R.J. Erdtsieck, H.A. Pols, N.K. Valk, B.M. van Ouwerkerk, S.W. Lamberts, P. Mulder, J.C. Birkenhager, Treatment of post-menopausal osteoporosis with a combination of growth hormone and pamidronate: a placebo controlled trial. Clin. Endocrinol. 43(5), 557–565 (1995)CrossRef
26.
Zurück zum Zitat J.P.T. Higgins, S. Green, Cochrane handbook for systematic reviews of interventions. version 5.1.0. The Cochrane Collaboration (2011) J.P.T. Higgins, S. Green, Cochrane handbook for systematic reviews of interventions. version 5.1.0. The Cochrane Collaboration (2011)
27.
Zurück zum Zitat S. Gonnelli, C. Cepollaro, M. Montomoli, L. Gennari, A. Montagnani, R. Palmieri, C. Gennari, Treatment of post-menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: a placebo controlled study. Clin. Endocrinol. 46(1), 55–61 (1997)CrossRef S. Gonnelli, C. Cepollaro, M. Montomoli, L. Gennari, A. Montagnani, R. Palmieri, C. Gennari, Treatment of post-menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: a placebo controlled study. Clin. Endocrinol. 46(1), 55–61 (1997)CrossRef
28.
Zurück zum Zitat J.F. Aloia, A. Vaswani, A. Kapoor, J.K. Yeh, S.H. Cohn, Treatment of osteoporosis with calcitonin, with and without growth hormone. Metabolism 34(2), 124–129 (1985)CrossRefPubMed J.F. Aloia, A. Vaswani, A. Kapoor, J.K. Yeh, S.H. Cohn, Treatment of osteoporosis with calcitonin, with and without growth hormone. Metabolism 34(2), 124–129 (1985)CrossRefPubMed
29.
Zurück zum Zitat J.F. Aloia, A. Vaswani, P.J. Meunier, C.M. Edouard, M.E. Arlot, J.K. Yeh, S.H. Cohn, Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin. Calcif. Tissue Int. 40(5), 253–259 (1987)CrossRefPubMed J.F. Aloia, A. Vaswani, P.J. Meunier, C.M. Edouard, M.E. Arlot, J.K. Yeh, S.H. Cohn, Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin. Calcif. Tissue Int. 40(5), 253–259 (1987)CrossRefPubMed
30.
Zurück zum Zitat T.B. Hansen, K. Brixen, N. Vahl, J.O. Jorgensen, J.S. Christiansen, L. Mosekilde, C. Hagen, Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. J. Clin. Endocrinol. Metab. 81(9), 3352–3359 (1996). https://doi.org/10.1210/jcem.81.9.8784096 PubMed T.B. Hansen, K. Brixen, N. Vahl, J.O. Jorgensen, J.S. Christiansen, L. Mosekilde, C. Hagen, Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. J. Clin. Endocrinol. Metab. 81(9), 3352–3359 (1996). https://​doi.​org/​10.​1210/​jcem.​81.​9.​8784096 PubMed
35.
Zurück zum Zitat D.B. Allen, P. Backeljauw, M. Bidlingmaier, B.M. Biller, M. Boguszewski, P. Burman, G. Butler, K. Chihara, J. Christiansen, S. Cianfarani, P. Clayton, D. Clemmons, P. Cohen, F. Darendeliler, C. Deal, D. Dunger, E.M. Erfurth, J.S. Fuqua, A. Grimberg, M. Haymond, C. Higham, K. Ho, A.R. Hoffman, A. Hokken-Koelega, G. Johannsson, A. Juul, J. Kopchick, P. Lee, M. Pollak, S. Radovick, L. Robison, R. Rosenfeld, R.J. Ross, L. Savendahl, P. Saenger, H. Toft Sorensen, K. Stochholm, C. Strasburger, A. Swerdlow, M. Thorner, GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur. J. Endocrinol. 174(2), P1–9 (2016). https://doi.org/10.1530/EJE-15-0873 CrossRefPubMed D.B. Allen, P. Backeljauw, M. Bidlingmaier, B.M. Biller, M. Boguszewski, P. Burman, G. Butler, K. Chihara, J. Christiansen, S. Cianfarani, P. Clayton, D. Clemmons, P. Cohen, F. Darendeliler, C. Deal, D. Dunger, E.M. Erfurth, J.S. Fuqua, A. Grimberg, M. Haymond, C. Higham, K. Ho, A.R. Hoffman, A. Hokken-Koelega, G. Johannsson, A. Juul, J. Kopchick, P. Lee, M. Pollak, S. Radovick, L. Robison, R. Rosenfeld, R.J. Ross, L. Savendahl, P. Saenger, H. Toft Sorensen, K. Stochholm, C. Strasburger, A. Swerdlow, M. Thorner, GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur. J. Endocrinol. 174(2), P1–9 (2016). https://​doi.​org/​10.​1530/​EJE-15-0873 CrossRefPubMed
Metadaten
Titel
Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis
verfasst von
Maya Barake
Asma Arabi
Nancy Nakhoul
Ghada El-Hajj Fuleihan
Sarah El Ghandour
Anne Klibanski
Nicholas A. Tritos
Publikationsdatum
13.10.2017
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1440-0

Weitere Artikel der Ausgabe 1/2018

Endocrine 1/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

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