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Use of Bisphosphonates in Genetic Diseases Other than Osteogenesis Imperfecta

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Bone Drugs in Pediatrics

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Abstract

Besides osteogenesis imperfecta, several genetic diseases may cause alterations in bone metabolism, with low bone mass, low bone strength, and fragility fractures. Some other diseases are instead characterized by bone formation outside the skeletal system (heterotopic ossification). Although little data are available, and mainly from case reports and not from controlled studies on significantly large samples, bisphosphonates seem to be effective to increase bone mass, reduce the risk of fractures, alleviate bone pain, and even, in some measure, hinder the formation of heterotopic bone. Only for the more common diseases, like Duchenne muscular dystrophy and cystic fibrosis, there are sufficient data to recommend the prudent use of BPs as a standard treatment of bone complications.

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Notes

  1. 1.

    According to the Pediatric Position Development Conference (PPDC) 2013 of the International Society of Clinical Densitometry (ISCD), the diagnosis of osteoporosis in children and adolescents should not be made on the basis of densitometric criteria alone. Osteoporosis can be diagnosed in the presence of one or more vertebral compression (crush) fractures, not attributable to local disease or high-energy trauma. In the absence of such fractures, a diagnosis of osteoporosis requires the presence of both a BMD Z-score ≤ −2.0 and a clinically significant fracture history (defined as “two or more long bone fractures by age 10 years” or “three or more long bone fractures at any age up to 19 years”). The ISCD PPDC 2013 document can be read at: http://www.iscd.org/2013-iscd-official-positions-pediatric/.

  2. 2.

    DXA measures an “areal” BMD (aBMD, i.e., BMC in g/cm2 of bone projection area) and not the true “volumetric” BMD (vBMD, i.e., BMC in g/cm3 of bone volume). For mathematical reasons, if two bones of equal vBMD (g/cm3) are analyzed with DXA, the smaller bone will have a lower aBMD than the larger bone; that is, DXA overestimates aBMD as bone size increases. For this reason, aBMD is unsuitable for the study of growing subjects, and a surrogate of vBMD, called “bone mineral apparent density” (BMAD, g/cm3), and its Z-score are preferred. The BMAD is calculated by assuming that the vertebral body is a cube or a cylinder, whose volume can be easily calculated from the projection height and width.

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  1. Bone Metabolism Unit, Istituto Auxologico Italiano IRCCS, Via L. Ariosto 13, 20145, Milano, Italy

    Maria Luisa Bianchi M.D.

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  1. Department of Orthopaedic Surgery, University of Texas Medical Branch, Galveston, Texas, USA

    Gordon L. Klein

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Bianchi, M.L. (2014). Use of Bisphosphonates in Genetic Diseases Other than Osteogenesis Imperfecta. In: Klein, G. (eds) Bone Drugs in Pediatrics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7436-5_6

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