Anabolic Therapy for the Treatment of Osteoporosis in Childhood
Purpose of Review
Numerous forms of osteoporosis in childhood are characterized by low bone turnover (for example, osteoporosis due to neuromuscular disorders and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to treat osteoporosis in the young, is associated with further reductions in bone turnover, raising concerns about the long-term safety and efficacy of such therapy. These observations have led to increasing interest in the role of anabolic therapy to treat pediatric osteoporosis.
While growth hormone and androgens appears to be relatively weak anabolic modulators of bone mass, emerging therapies targeting bone formation pathways (anti-transforming growth factor beta antibody and anti-sclerostin antibody) hold considerable promise. Teriparatide remains an attractive option that merits formal study for patients post-epiphyseal fusion, although it must be considered that adult studies have shown its effect is blunted when administered following bisphosphonate therapy. Mechanical stimulation of bone through whole body vibration therapy appears to be much less effective than bisphosphonate therapy for treating osteoporosis in children.
New anabolic therapies which target important pathways in skeletal metabolism merit further study in children, including their effects on fracture risk reduction and after treatment discontinuation.
KeywordsChildren Anabolic therapy Bone Fractures Growth hormone Parathyroid hormone Androgen therapy Testosterone Anti-sclerostin antibody Anti-TGF-beta antibody Whole body vibration therapy
Bone mineral content
Bone mineral density
Dual energy x-ray absorptiometry
Duchenne muscular dystrophy
Growth hormone deficiency
Osteoporosis pseudoglioma syndrome
Peripheral quantitative computed tomography
Transforming growth factor beta
Whole body vibration
Dr. Ward is supported by a Research Chair Award from the University of Ottawa.
Compliance with Ethical Standards
Conflict of Interest
Leanne Ward is participating in clinical trials with AMGEN, outside the submitted work. Frank Rauch declares no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 5.Misof BM, Roschger P, McMillan HJ, Ma J, Klaushofer K, Rauch F, et al. Histomorphometry and bone matrix mineralization before and after bisphosphonate treatment in boys with Duchenne muscular dystrophy: a paired transiliac biopsy study. J Bone Miner Res. 2016;31(5):1060–9.PubMedCrossRefGoogle Scholar
- 13.Marini JC, Hopkins E, Glorieux FH, Chrousos GP, Reynolds JC, Gundberg CM, et al. Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen. J Bone Miner Res. 2003;18(2):237–43.PubMedCrossRefGoogle Scholar
- 15.Frittoli RB, Longhi BS, Silva AM, Filho AAB, Monteiro M, Appenzeller S. Erratum to “Effects of the use of growth hormone in children, adolescents with juvenile idiopathic arthritis: a systematic review” (Rev Bras Reumatol. 2017;57(2):100-106). Rev Bras Reumatol Engl Ed. 2017;57(5):500.PubMedCrossRefGoogle Scholar
- 17.Ward LM, Kinnett K, Bonewald L. Proceedings of a Parent Project Muscular Dystrophy Bone Health Workshop: morbidity due to osteoporosis in DMD: the path forward May 12–13, 2016, Bethesda, Maryland, USA. Neuromuscul Disord. 2017.Google Scholar
- 26.Camacho PM, Petak SM, Binkley N, Clarke BL, Harris ST, Hurley DL, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2016. Endocr Pract. 2016;22(Suppl 4):1–42.PubMedCrossRefGoogle Scholar
- 32.Ma J, McMillan HJ, Karaguzel G, Goodin C, Wasson J, Matzinger MA, et al. The time to and determinants of first fractures in boys with Duchenne muscular dystrophy. Osteoporos Int. 2017;28(2):597–608.Google Scholar
- 35.Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, et al. Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res. 2008;23(10):1591–600.PubMedCrossRefGoogle Scholar
- 38.• Leonard MB, Shults J, Long J, Baldassano RN, Brown JK, Hommel K, et al. Effect of low-magnitude mechanical stimuli on bone density and structure in pediatric Crohn's disease: a randomized placebo-controlled trial. J Bone Miner Res. 2016;31(6):1177–88. Even though the study outcome is essentially negative, this report provides an excellent template of how to design, conduct, evaluate and report whole-body vibration studies.PubMedPubMedCentralCrossRefGoogle Scholar
- 45.• Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532–43. This randomized, placebo-controlled study examines the effect of romozosumab on women with post-menopausal osteoporosis, showing a significant reduction in all fractures rates but similar adverse effect frequencies. PubMedCrossRefGoogle Scholar
- 61.• Wehmeyer C, Frank S, Beckmann D, Bottcher M, Cromme C, Konig U, et al. Sclerostin inhibition promotes TNF-dependent inflammatory joint destruction. Sci Transl Med. 2016;8(330):330ra35. Sclerostin is generally thought to be a bone-specific protein, but this study shows that in pathological situations anti-sclerostin treatments may have unexpected adverse effects. In a mouse model of rheumatoid arthritis, sclerostin inhibition led to increased cartilage destruction.PubMedCrossRefGoogle Scholar
- 64.Recknor CP, Recker RR, Benson CT, Robins DA, Chiang AY, Alam J, et al. The effect of discontinuing treatment with blosozumab: follow-up results of a phase 2 randomized clinical trial in postmenopausal women with low bone mineral density. J Bone Miner Res. 2015;30(9):1717–25.PubMedCrossRefGoogle Scholar
- 65.Janssens K, Vanhoenacker F, Bonduelle M, Verbruggen L, Van Maldergem L, Ralston S, et al. Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet. 2006;43(1):1–11.PubMedPubMedCentralCrossRefGoogle Scholar
- 67.• Grafe I, Yang T, Alexander S, Homan EP, Lietman C, Jiang MM, et al. Excessive transforming growth factor-beta signaling is a common mechanism in osteogenesis imperfecta. Nat Med. 2014;20(6):670–5. This study shows that altered TGFβ matrix-cell signaling is a primary mechanism in the pathogenesis of OI, and could be a promising target for the treatment of OI. PubMedPubMedCentralCrossRefGoogle Scholar