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Erschienen in: Current Osteoporosis Reports 2/2014

01.06.2014 | Muscle and Bone (L Bonewald and M Harrick, Section Editors)

Therapies for Musculoskeletal Disease: Can we Treat Two Birds with One Stone?

verfasst von: Christian M. Girgis, Nancy Mokbel, Douglas J. DiGirolamo

Erschienen in: Current Osteoporosis Reports | Ausgabe 2/2014

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Abstract

Musculoskeletal diseases are highly prevalent with staggering annual health care costs across the globe. The combined wasting of muscle (sarcopenia) and bone (osteoporosis)—both in normal aging and pathologic states—can lead to vastly compounded risk for fracture in patients. Until now, our therapeutic approach to the prevention of such fractures has focused solely on bone, but our increasing understanding of the interconnected biology of muscle and bone has begun to shift our treatment paradigm for musculoskeletal disease. Targeting pathways that centrally regulate both bone and muscle (eg, GH/IGF-1, sex steroids, etc.) and newly emerging pathways that might facilitate communication between these 2 tissues (eg, activin/myostatin) might allow a greater therapeutic benefit and/or previously unanticipated means by which to treat these frail patients and prevent fracture. In this review, we will discuss a number of therapies currently under development that aim to treat musculoskeletal disease in precisely such a holistic fashion.
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Zurück zum Zitat Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335–45. doi:10.1016/S1470-2045(13)70055-X. This clinical trial of enobosarm, a nonsteroidal SARM, showed significant increases in lean body mass but no effect in bone mineral density in patients with cancer cachexia. A phase 3 trial is currently underway.PubMed Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335–45. doi:10.​1016/​S1470-2045(13)70055-X. This clinical trial of enobosarm, a nonsteroidal SARM, showed significant increases in lean body mass but no effect in bone mineral density in patients with cancer cachexia. A phase 3 trial is currently underway.PubMed
71.
Zurück zum Zitat Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68(1):87–95. doi:10.1093/gerona/gls078.PubMed Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68(1):87–95. doi:10.​1093/​gerona/​gls078.PubMed
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Zurück zum Zitat Papanicolaou DA, Ather SN, Zhu H, Zhou Y, Lutkiewicz J, Scott BB, et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J Nutr Health Aging. 2013;17(6):533–43. doi:10.1007/s12603-013-0335-x. The steroidal SARM, MK-0773, resulted in significant increases in lean body mass in frail elderly women but this did not translate to improvements in muscle strength.PubMed Papanicolaou DA, Ather SN, Zhu H, Zhou Y, Lutkiewicz J, Scott BB, et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J Nutr Health Aging. 2013;17(6):533–43. doi:10.​1007/​s12603-013-0335-x. The steroidal SARM, MK-0773, resulted in significant increases in lean body mass in frail elderly women but this did not translate to improvements in muscle strength.PubMed
73.•
Zurück zum Zitat Girgis CM, Clifton-Bligh RJ, Hamrick MW, Holick MF, Gunton JE. The roles of Vitamin D in skeletal muscle: form, function, and metabolism. Endocr Rev. 2013;34:33–83. doi:10.1210/er.2012-1012. This review summarizes effects of vitamin D in skeletal muscle from animal, cell and human studies.PubMed Girgis CM, Clifton-Bligh RJ, Hamrick MW, Holick MF, Gunton JE. The roles of Vitamin D in skeletal muscle: form, function, and metabolism. Endocr Rev. 2013;34:33–83. doi:10.​1210/​er.​2012-1012. This review summarizes effects of vitamin D in skeletal muscle from animal, cell and human studies.PubMed
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Zurück zum Zitat Amling M, Priemel M, Holzmann T, Chapin K, Rueger JM, Baron R, et al. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology. 1999;140(11):4982–7.PubMed Amling M, Priemel M, Holzmann T, Chapin K, Rueger JM, Baron R, et al. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology. 1999;140(11):4982–7.PubMed
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Zurück zum Zitat Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys. 2012;523(1):123–33. doi:10.1016/j.abb.2012.04.001. This article examines the tissue distribution of VDR, including organs where its presence is controversial such as liver and skeletal muscle.PubMed Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys. 2012;523(1):123–33. doi:10.​1016/​j.​abb.​2012.​04.​001. This article examines the tissue distribution of VDR, including organs where its presence is controversial such as liver and skeletal muscle.PubMed
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Zurück zum Zitat Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P, et al. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012;122(5):1803–15. doi:10.1172/JCI45890.PubMedCentralPubMed Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P, et al. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012;122(5):1803–15. doi:10.​1172/​JCI45890.PubMedCentralPubMed
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Zurück zum Zitat Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, et al. Vitamin D receptor in osteoblasts is a negative regulator of bone mass control. Endocrinology. 2013;154(3):1008–20. doi:10.1210/en.2012-1542.PubMed Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, et al. Vitamin D receptor in osteoblasts is a negative regulator of bone mass control. Endocrinology. 2013;154(3):1008–20. doi:10.​1210/​en.​2012-1542.PubMed
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Zurück zum Zitat Lam NN, Triliana R, Sawyer RK, Atkins GJ, Morris HA, O'Loughlin PD, et al. Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone loss during vitamin D-deficiency. J Steroid Biochem Mol Biol. 2014. doi:10.1016/j.jsbmb.2014.01.002.PubMed Lam NN, Triliana R, Sawyer RK, Atkins GJ, Morris HA, O'Loughlin PD, et al. Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone loss during vitamin D-deficiency. J Steroid Biochem Mol Biol. 2014. doi:10.​1016/​j.​jsbmb.​2014.​01.​002.PubMed
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Zurück zum Zitat Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. 2003;144(12):5138–44. doi:10.1210/en.2003-0502.PubMed Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. 2003;144(12):5138–44. doi:10.​1210/​en.​2003-0502.PubMed
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Zurück zum Zitat Girgis CM, Clifton-Bligh RJ, Mokbel N, Cheng K, Gunton JE. Vitamin D signaling regulates proliferation, differentiation and myotube size in C2C12 skeletal muscle cells. Endocrinology. 2014;155(2):347–57. doi:10.1210/en.2013-1205.PubMed Girgis CM, Clifton-Bligh RJ, Mokbel N, Cheng K, Gunton JE. Vitamin D signaling regulates proliferation, differentiation and myotube size in C2C12 skeletal muscle cells. Endocrinology. 2014;155(2):347–57. doi:10.​1210/​en.​2013-1205.PubMed
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Zurück zum Zitat Lee SG, Lee YH, Kim KJ, Lee W, Kwon OH, Kim JH. Additive association of vitamin D insufficiency and sarcopenia with low femoral bone mineral density in noninstitutionalized elderly population: the Korea National Health and Nutrition Examination Surveys 2009–2010. Osteoporos Int. 2013;24(11):2789–99. doi:10.1007/s00198-013-2378-6.PubMed Lee SG, Lee YH, Kim KJ, Lee W, Kwon OH, Kim JH. Additive association of vitamin D insufficiency and sarcopenia with low femoral bone mineral density in noninstitutionalized elderly population: the Korea National Health and Nutrition Examination Surveys 2009–2010. Osteoporos Int. 2013;24(11):2789–99. doi:10.​1007/​s00198-013-2378-6.PubMed
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Zurück zum Zitat Snijder MB, van Schoor NM, Pluijm SM, van Dam RM, Visser M, Lips P. Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J Clin Endocrinol Metab. 2006;91(8):2980–5. doi:10.1210/jc.2006-0510.PubMed Snijder MB, van Schoor NM, Pluijm SM, van Dam RM, Visser M, Lips P. Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J Clin Endocrinol Metab. 2006;91(8):2980–5. doi:10.​1210/​jc.​2006-0510.PubMed
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Zurück zum Zitat Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293(18):2257–64. doi:10.1001/jama.293.18.2257.PubMed Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293(18):2257–64. doi:10.​1001/​jama.​293.​18.​2257.PubMed
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Zurück zum Zitat Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. 2007;55(2):234–9. doi:10.1111/j.1532-5415.2007.01048.x.PubMed Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. 2007;55(2):234–9. doi:10.​1111/​j.​1532-5415.​2007.​01048.​x.PubMed
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Zurück zum Zitat Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669–83. doi:10.1056/NEJMoa055218.PubMed Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669–83. doi:10.​1056/​NEJMoa055218.PubMed
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Zurück zum Zitat Ceglia L, Niramitmahapanya S, Morais MD, Rivas DA, Harris SS, Bischoff-Ferrari H, et al. A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab. 2013. doi:10.1210/jc.2013–2820. This RCT of 21 older women showed an increase in myonuclear VDR and muscle fiber size amongst those receiving vitamin D supplementation (4000 IU d for 4 months). However, functional parameters were unchanged, possibly due to the small sample size. Ceglia L, Niramitmahapanya S, Morais MD, Rivas DA, Harris SS, Bischoff-Ferrari H, et al. A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab. 2013. doi:10.​1210/​jc.​2013–2820. This RCT of 21 older women showed an increase in myonuclear VDR and muscle fiber size amongst those receiving vitamin D supplementation (4000 IU d for 4 months). However, functional parameters were unchanged, possibly due to the small sample size.
90.•
Zurück zum Zitat Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815–22. doi:10.1001/jama.2010.594. This well-known RCT of 2256 community-dwelling older women reported an increased risk of falls and fractures in the 3 months following vitamin D mega-supplementation (500,000 IU oral).PubMed Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815–22. doi:10.​1001/​jama.​2010.​594. This well-known RCT of 2256 community-dwelling older women reported an increased risk of falls and fractures in the 3 months following vitamin D mega-supplementation (500,000 IU oral).PubMed
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Zurück zum Zitat Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8. doi:10.1210/jc.2010-2704. This article summarizes the IOM recommendations for 25OHD target levels (50 nmol/L) and daily vitamin D doses (800 IU in adults >70years). Extra-skeletal benefits of vitamin D were reportedly “not yet compelling”.PubMedCentralPubMed Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8. doi:10.​1210/​jc.​2010-2704. This article summarizes the IOM recommendations for 25OHD target levels (50 nmol/L) and daily vitamin D doses (800 IU in adults >70years). Extra-skeletal benefits of vitamin D were reportedly “not yet compelling”.PubMedCentralPubMed
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Zurück zum Zitat Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi:10.1210/jc.2011-0385. In contrast to the IOM recommendations, the Endocrine society advocated a higher 25OHD target level of 75 nmol/L and daily doses of at least 1500–2000 IU in the older age-group.PubMed Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi:10.​1210/​jc.​2011-0385. In contrast to the IOM recommendations, the Endocrine society advocated a higher 25OHD target level of 75 nmol/L and daily doses of at least 1500–2000 IU in the older age-group.PubMed
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Zurück zum Zitat Korpelainen R, Keinanen-Kiukaanniemi S, Heikkinen J, Vaananen K, Korpelainen J. Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention. Osteoporos Int. 2006;17(1):109–18. doi:10.1007/s00198-005-1924-2.PubMed Korpelainen R, Keinanen-Kiukaanniemi S, Heikkinen J, Vaananen K, Korpelainen J. Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention. Osteoporos Int. 2006;17(1):109–18. doi:10.​1007/​s00198-005-1924-2.PubMed
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Zurück zum Zitat Winters-Stone KM, Dobek J, Nail L, Bennett JA, Leo MC, Naik A, et al. Strength training stops bone loss and builds muscle in postmenopausal breast cancer survivors: a randomized, controlled trial. Breast Cancer Res Treat. 2011;127(2):447–56. doi:10.1007/s10549-011-1444-z.PubMedCentralPubMed Winters-Stone KM, Dobek J, Nail L, Bennett JA, Leo MC, Naik A, et al. Strength training stops bone loss and builds muscle in postmenopausal breast cancer survivors: a randomized, controlled trial. Breast Cancer Res Treat. 2011;127(2):447–56. doi:10.​1007/​s10549-011-1444-z.PubMedCentralPubMed
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Zurück zum Zitat Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006;21(9):1464–74. doi:10.1359/jbmr.060612.PubMed Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006;21(9):1464–74. doi:10.​1359/​jbmr.​060612.PubMed
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Zurück zum Zitat Dudley-Javoroski S, Shields RK. Muscle and bone plasticity after spinal cord injury: review of adaptations to disuse and to electrical muscle stimulation. J Rehabil Res Dev. 2008;45(2):283–96.PubMedCentralPubMed Dudley-Javoroski S, Shields RK. Muscle and bone plasticity after spinal cord injury: review of adaptations to disuse and to electrical muscle stimulation. J Rehabil Res Dev. 2008;45(2):283–96.PubMedCentralPubMed
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Zurück zum Zitat Serrano-Urrea R, Garcia-Meseguer MJ. Malnutrition in an elderly population without cognitive impairment living in nursing homes in Spain: study of prevalence using the Mini Nutritional Assessment test. Gerontology. 2013;59(6):490–8. doi:10.1159/000351763.PubMed Serrano-Urrea R, Garcia-Meseguer MJ. Malnutrition in an elderly population without cognitive impairment living in nursing homes in Spain: study of prevalence using the Mini Nutritional Assessment test. Gerontology. 2013;59(6):490–8. doi:10.​1159/​000351763.PubMed
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Zurück zum Zitat Berner LA, Becker G, Wise M, Doi J. Characterization of dietary protein among older adults in the United States: amount, animal sources, and meal patterns. J Acad Nutr Diet. 2013;113(6):809–15. doi:10.1016/j.jand.2013.01.014.PubMed Berner LA, Becker G, Wise M, Doi J. Characterization of dietary protein among older adults in the United States: amount, animal sources, and meal patterns. J Acad Nutr Diet. 2013;113(6):809–15. doi:10.​1016/​j.​jand.​2013.​01.​014.PubMed
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Zurück zum Zitat Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr. 2008;87(1):150–5.PubMed Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr. 2008;87(1):150–5.PubMed
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Zurück zum Zitat Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev. 2009(2):CD003288. doi:10.1002/14651858.CD003288.pub3. Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev. 2009(2):CD003288. doi:10.​1002/​14651858.CD003288.pub3.
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Zurück zum Zitat Miller CT, Fraser SF, Levinger I, Straznicky NE, Dixon JB, Reynolds J, et al. The effects of exercise training in addition to energy restriction on functional capacities and body composition in obese adults during weight loss: a systematic review. PLoS One. 2013;8(11):e81692. doi:10.1371/journal.pone.0081692.PubMedCentralPubMed Miller CT, Fraser SF, Levinger I, Straznicky NE, Dixon JB, Reynolds J, et al. The effects of exercise training in addition to energy restriction on functional capacities and body composition in obese adults during weight loss: a systematic review. PLoS One. 2013;8(11):e81692. doi:10.​1371/​journal.​pone.​0081692.PubMedCentralPubMed
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Zurück zum Zitat Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657–66. doi:10.1016/S0140-6736(07)61342-7.PubMed Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657–66. doi:10.​1016/​S0140-6736(07)61342-7.PubMed
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Zurück zum Zitat McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997;387(6628):83–90. doi:10.1038/387083a0.PubMed McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997;387(6628):83–90. doi:10.​1038/​387083a0.PubMed
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Zurück zum Zitat Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004;350(26):2682–8. doi:10.1056/NEJMoa040933.PubMed Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004;350(26):2682–8. doi:10.​1056/​NEJMoa040933.PubMed
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Zurück zum Zitat Han DS, Chen YM, Lin SY, Chang HH, Huang TM, Chi YC, et al. Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis. Clin Endocrinol. 2011;75(6):857–63. doi:10.1111/j.1365-2265.2011.04120.x. Han DS, Chen YM, Lin SY, Chang HH, Huang TM, Chi YC, et al. Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis. Clin Endocrinol. 2011;75(6):857–63. doi:10.​1111/​j.​1365-2265.​2011.​04120.​x.
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Zurück zum Zitat Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci U S A. 1998;95(25):14938–43.PubMedCentralPubMed Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci U S A. 1998;95(25):14938–43.PubMedCentralPubMed
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Zurück zum Zitat Zhang ZL, He JW, Qin YJ, Hu YQ, Li M, Zhang H, et al. Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families. Osteoporos Int. 2008;19(1):39–47. doi:10.1007/s00198-007-0435-8.PubMed Zhang ZL, He JW, Qin YJ, Hu YQ, Li M, Zhang H, et al. Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families. Osteoporos Int. 2008;19(1):39–47. doi:10.​1007/​s00198-007-0435-8.PubMed
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Zurück zum Zitat Digirolamo D SV, Clemens T, Lee S-J. Systemic administration of soluble 483 activin receptors produces differential anabolic effects in muscle and bone in mice. J Bone Miner Res. 2011;1167 (Suppl.). This abstract presented at ASBMR meeting 2011 reported direct effects of activin receptor signaling in osteoblasts. Mice treated with ActRII-Fc fusion proteins showed both increases in muscle (15%–40%) and trabecular (~13%) bone over 4 weeks. Digirolamo D SV, Clemens T, Lee S-J. Systemic administration of soluble 483 activin receptors produces differential anabolic effects in muscle and bone in mice. J Bone Miner Res. 2011;1167 (Suppl.). This abstract presented at ASBMR meeting 2011 reported direct effects of activin receptor signaling in osteoblasts. Mice treated with ActRII-Fc fusion proteins showed both increases in muscle (15%–40%) and trabecular (~13%) bone over 4 weeks.
119.•
Zurück zum Zitat Bowser M, Herberg S, Arounleut P, Shi X, Fulzele S, Hill WD, et al. Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells. Exp Gerontol. 2013;48(2):290–7. doi:10.1016/j.exger.2012.11.004. This study examined age-related differences in the expression and activity of myostatin, activin A, and follistatin in mice. Myostatin was particularly important in the impaired proliferative capacity of aged muscle and bone cells, making it an appropriate therapeutic target in treating sarcopenia-osteoporosis.PubMedCentralPubMed Bowser M, Herberg S, Arounleut P, Shi X, Fulzele S, Hill WD, et al. Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells. Exp Gerontol. 2013;48(2):290–7. doi:10.​1016/​j.​exger.​2012.​11.​004. This study examined age-related differences in the expression and activity of myostatin, activin A, and follistatin in mice. Myostatin was particularly important in the impaired proliferative capacity of aged muscle and bone cells, making it an appropriate therapeutic target in treating sarcopenia-osteoporosis.PubMedCentralPubMed
120.
Zurück zum Zitat Koncarevic A, Cornwall-Brady M, Pullen A, Davies M, Sako D, Liu J, et al. A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health. Endocrinology. 2010;151(9):4289–300. doi:10.1210/en.2010-0134.PubMed Koncarevic A, Cornwall-Brady M, Pullen A, Davies M, Sako D, Liu J, et al. A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health. Endocrinology. 2010;151(9):4289–300. doi:10.​1210/​en.​2010-0134.PubMed
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Zurück zum Zitat Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA, Ahima RS, et al. Functional improvement of dystrophic muscle by myostatin blockade. Nature. 2002;420(6914):418–21. doi:10.1038/nature01154.PubMed Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA, Ahima RS, et al. Functional improvement of dystrophic muscle by myostatin blockade. Nature. 2002;420(6914):418–21. doi:10.​1038/​nature01154.PubMed
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Zurück zum Zitat Chiu CS, Peekhaus N, Weber H, Adamski S, Murray EM, Zhang HZ, et al. Increased muscle force production and bone mineral density in ActRIIB-Fc-treated mature rodents. J Gerontol A Biol Sci Med Sci. 2013;68(10):1181–92. doi:10.1093/gerona/glt030. Aged mice treated with ActRIIB-Fc fusion protein showed enhanced muscle size and function after 3 days. Similar features were observed in hypogonadal male mice (ie, orchidectomized) and improvements in bone mineral density were also reported.PubMed Chiu CS, Peekhaus N, Weber H, Adamski S, Murray EM, Zhang HZ, et al. Increased muscle force production and bone mineral density in ActRIIB-Fc-treated mature rodents. J Gerontol A Biol Sci Med Sci. 2013;68(10):1181–92. doi:10.​1093/​gerona/​glt030. Aged mice treated with ActRIIB-Fc fusion protein showed enhanced muscle size and function after 3 days. Similar features were observed in hypogonadal male mice (ie, orchidectomized) and improvements in bone mineral density were also reported.PubMed
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Metadaten
Titel
Therapies for Musculoskeletal Disease: Can we Treat Two Birds with One Stone?
verfasst von
Christian M. Girgis
Nancy Mokbel
Douglas J. DiGirolamo
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Current Osteoporosis Reports / Ausgabe 2/2014
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-014-0204-5

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