Therapeutic management of hypophosphatemic rickets from infancy to adulthood

Abstract

In children, hypophosphatemic rickets (HR) is revealed by delayed walking, waddling gait, leg bowing, enlarged cartilages, bone pain, craniostenosis, spontaneous dental abscesses, and growth failure. If undiagnosed during childhood, patients with hypophosphatemia present with bone and/or joint pain, fractures, mineralization defects such as osteomalacia, entesopathy, severe dental anomalies, hearing loss, and fatigue. Healing rickets is the initial endpoint of treatment in children. Therapy aims at counteracting consequences of FGF23 excess, i.e. oral phosphorus supplementation with multiple daily intakes to compensate for renal phosphate wasting and active vitamin D analogs (alfacalcidol or calcitriol) to counter the 1,25-diOH-vitamin D deficiency. Corrective surgeries for residual leg bowing at the end of growth are occasionally performed. In absence of consensus regarding indications of the treatment in adults, it is generally accepted that medical treatment should be reinitiated (or maintained) in symptomatic patients to reduce pain, which may be due to bone microfractures and/or osteomalacia. In addition to the conventional treatment, optimal care of symptomatic patients requires pharmacological and non-pharmacological management of pain and joint stiffness, through appropriated rehabilitation. Much attention should be given to the dental and periodontal manifestations of HR. Besides vitamin D analogs and phosphate supplements that improve tooth mineralization, rigorous oral hygiene, active endodontic treatment of root abscesses and preventive protection of teeth surfaces are recommended. Current outcomes of this therapy are still not optimal, and therapies targeting the pathophysiology of the disease, i.e. FGF23 excess, are desirable. In this review, medical, dental, surgical, and contributions of various expertises to the treatment of HR are described, with an effort to highlight the importance of coordinated care.

Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms

“…Therapy with phosphate salts and vitamin D analogs aim at reducing bone pain, improving dentition, correcting leg deformities, improving adult height and decreasing the number of surgeries (2,3). Initiation at early ages is recommended as the early initiation of treatment optimises final body height results (2,3).…”

“…Adult patients with XLH (XLH adults) can be affected not only by skeletal complications related to spontaneous fractures because of persistent osteomalacia but also early osteoarthritis and enthesopathies, for which the severity of symptoms and of structural involvement is variable (3,4,5,6). The disease outcome in adults remains inadequately described.…”

Comparative study of children with calciopaenic and phosphopaenic rickets seen at Chris Hani Baragwanath Hospital

“…1,3,4,8 The commonest cause of calciopaenic rickets is vitamin D deficiency which is easily corrected by oral administration of vitamin D. 3 X-linked hypophosphataemic rickets is the most common form of phosphopaenic rickets and is currently treated with calcitriol and phosphate supplements. 9,10 In South Africa, there are little published data on the prevalence and presentation of the different types of rickets in children. The clinical, biochemical and radiological differences between calciopaenic and phosphopaenic rickets may not be easily recognised by the attending health care workers in primary and secondary health care facilities.…”

Dental Management of Hypophosphatemic Vitamin D Resistant Rickets

“…The enamel in these cases was reported to be normal but thinner contrary to defective dentin tissue (4,11). However, sometimes, enamel cracks (18,19) and enamel hypoplasia (3,18,20) can be observed in patients.…”