Cortical and Trabecular Bone Density in X-Linked Hypophosphatemic Rickets

Abstract

Context: X-linked hypophosphatemic rickets is caused by mutations in PHEX. Even though the disease is characterized by disordered skeletal mineralization, detailed bone densitometric studies are lacking.Objective: The aim of the study was to assess volumetric bone mineral density (vBMD) in X-linked hypophosphatemic rickets using forearm peripheral quantitative computed tomography. Setting:The study was conducted in the metabolic bone clinic of a pediatric orthopedic hospital.Patients: Thirty-four patients (age, 6 to 60 years; 24 female) with PHEX mutations were studied, of whom 7 children (age, 6 to 11 years) were actively being treated with calcitriol and phosphate supplementation. Twenty-one patients (age, 16 to 40 years) had received the same therapy before but had discontinued the treatment; 6 patients (age, 12 to 60 years) had never received this treatment. Main Outcome Measures: Trabecular and cortical vBMD of the radius.Results: Trabecular vBMD was elevated (mean age-specific and sex-specific z-score: ϩ1.0) when all patients were analyzed together, due to very high results in currently treated patients (mean z-score: ϩ2.4) and slightly above-average mean values in the other patients. Cortical vBMD was low when the entire cohort was analyzed together (mean z-score: Ϫ3.3), but was higher in currently treated patients (mean z-score: Ϫ1.3) than in patients who had discontinued therapy (mean zscore: Ϫ3.8) or who had never been treated (mean z-score: Ϫ4.1). Conclusions:Patients with PHEX mutations have elevated trabecular vBMD at the distal radius while receiving calcitriol and phosphate supplementation, but low cortical vBMD at the radius diaphysis. Low cortical vBMD presumably reflects the underlying mineralization defect that is not entirely corrected by current treatment approaches. (J Clin Endocrinol Metab 98: E954 -E961, 2013) H ereditary hypophosphatemic rickets is characterized by hypophosphatemia due to renal phosphate wasting, resulting in leg deformities and short stature (1, 2). Hypophosphatemic rickets is most commonly caused by mutations in the phosphate-regulating endopeptidase gene (PHEX), transmitted as an X-linked trait (X-linked hypophosphatemic rickets, XLH) (1, 3, 4).The current treatment for XLH consists of oral phosphate supplementation and calcitriol and aims at maximizing growth and preventing bone deformities (1, 2). Because these main benefits are dependent on skeletal growth and the treatment schedule is quite burdensome, therapy is often discontinued once final height is achieved. Abbreviations: BMD, bone mineral density; LS-aBMD, lumbar spine areal bone mineral density; pQCT, peripheral quantitative computed tomography; vBMD, volumetric bone mineral density; XLH, X-linked hypophosphatemic rickets.

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“…This outcome has also been observed in adults during DXA examination of the lumbar spine [107]. Bone mineral content was significantly higher in the XLH cohort in a pQCT study conducted in children, adolescents and adults with XLH [108]. In pQCT, XLH patients appear to have elevated trabecular volumetric bone mineral density (vBMD) at the distal radius while receiving calcitriol and phosphate supplementation but low cortical vBMD at the radial diaphysis.…”

“…In pQCT, XLH patients appear to have elevated trabecular volumetric bone mineral density (vBMD) at the distal radius while receiving calcitriol and phosphate supplementation but low cortical vBMD at the radial diaphysis. Low cortical vBMD presumably reflects the underlying mineralisation defect that is not entirely corrected by current treatment approaches [108]. However, XLH patients have a muscle function deficit in the lower extremities, even if bone mass and size are increased at the distal tibia [109].…”

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“…For example, in X-linked hypophosphatemic rickets, which is caused by phosphate-regulating endopeptidase homolog, X-linked (PHEX) mutations, the bone matrix surrounding osteocytes is hypomineralized, but overall bone mass is paradoxically increased (14). In osteogenesis imperfecta, which is caused by mutations in collagen type Iencoding genes, osteocyte density is conspicuously increased, and bone mass is typically very low (15).…”

Magnetic Resonance Imaging–Measured Bone Marrow Adipose Tissue Area Is Inversely Related to Cortical Bone Area in Children and Adolescents Aged 5–18 Years

“…Children, however, are more likely to fracture the cortical-rich appendicular skeleton as compared to adults (19). Specific pediatric metabolic bone disorders, such as X-linked hypophosphatemic rickets and chronic kidney disease (CKD), illustrate the importance of cortical bone parameters in pediatric populations (20). Children with CKD have decreased cortical volumetric bone mineral density as measured by peripheral quantitative computed tomography (21).…”