Current and Emerging Therapies for Pediatric Bone Diseases
- PDF / 1,025,478 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 71 Downloads / 217 Views
REVIEW ARTICLE
Current and Emerging Therapies for Pediatric Bone Diseases Supamit Ukarapong 1
&
Tossaporn Seeherunvong 1 & Gary Berkovitz 1
Published online: 15 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Most pediatric bone diseases result either from mutations of the essential genes for bone development or from abnormalities of mineral homeostasis. With an increase in non-invasive techniques to measure bone mineral density, the number of children with apparent low bone mineral density is rising. Furthermore, a new classification system proposed by the International Society for Clinical Densitometry now considers osteoporosis a valid diagnosis in children. Osteoporosis is a particular problem among children with conditions such as muscular dystrophy, immobilization, and chronic liver diseases and those who received a prolonged course of glucocorticoids. Pharmacologic agents for treatment of osteoporosis were developed primarily to prevent fragility fractures in postmenopausal women, and studies of their efficacy and safety in children are limited. Recent advances have seen new therapies for bone diseases in children; some of these conditions were deemed incurable in the past. This article reviews data regarding mechanism of action, safety, and efficacy of four bone drugs in pediatric patients. These are (1) zoledronic acid, a long-acting bisphosphonate; (2) denosumab, a RANKL inhibitor; (3) asfotase alfa, a synthetic alkaline phosphatase; and (4) burosumab, a monoclonal antibody against FGF23. Keywords Bone disease . Osteoporosis . Zoledronic acid . Denosumab . Asfotase alfa . Burosumab
Introduction Bone disorders in children compresses into two groups: (1) bone disorders caused by gene mutations that disrupt normal bone development and (2) metabolic bone disorders related to chronic illness or disuse osteopathy. The first group of bone disorders is further classified into dysostoses, skeletal dysplasias, and osteolysis syndromes [1]. Dysostoses result from mutations of genes expressed during skeletal organogenesis. Examples of these diseases include Holt-Oram (TBX5 mutation) and Cousin syndrome (TBX15 mutation). Disruptions of genes expressed during both organogenesis and in postnatal life are responsible for skeletal dysplasias. These conditions are further divided into primary and secondary skeletal dysplasias [1]. In primary skeletal dysplasias, the formation of skeletal tissues is disrupted due to the mutations of genes that are expressed in these tissues, while the abnormalities of external factors such as mineral homeostasis cause secondary * Supamit Ukarapong [email protected] 1
Division of Pediatric Endocrinology, University of Miami, Miller School of Medicine, 1601 NW 12th Avenue Suite 3044A, Miami, FL 33136, USA
skeletal dysplasias [1, 2]. Osteogenesis imperfecta (OI) is the best-known example of primary skeletal dysplasias. Hypophosphatasia and hypophosphatemic rickets are examples of secondary skeletal dysplasias [1, 2]. The third group of ge
Data Loading...
