Bone Abstracts

Background: X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia, bone deformities, and growth retardation. Conventional treatment of XLH with oral phosphate supplementation and high doses of vitamin D fails to normalize linear growth and adult stature remains disproportionately short. Few studies report on the use of recombinant human growth hormone (rhGH) therapy in pre-pubertal children with XLH.

Presenting problem: Two brothers were diagnosed clinically at infancy with XLH. Genetic analysis confirmed a frameshift mutation in the PHEX gene consistent with XLH. At endocrine referral extreme short stature (−3.7 SDS and −2.5 SDS) and an elevated upper segment/lower segment ratio were revealed.

Clinical management: Since treatment with alfacalcidol, phosphate and vitamin D failed to improve growth velocity, the GH axis was tested and GH reserve was normal. Both siblings underwent osteotomy for correction of their limb deformities (11.3 years and 10.8 years) with a beneficial effect on height-SDS (−3.7 to −2.4 and −2.5 to −1.9). Due to short stature at initiation of puberty and predicted compromised final height despite adherence to conventional therapy and osteotomy, rhGH therapy was initiated. Twelve-month rhGH treatment (0.05 mg/kg per d) initiated one year after surgical correction - improved height-SDS (−2.4 to −1.8 and −1.9 to −0.9). BMI centile remained stable 75%; U/L ratio (increased from 1.08 to 1.18 (within normal range) and remained stable 1.25 (increased)); pubertal stage advanced from Tanner 2 to 3 in both siblings and as expected IGF-1 levels increased (less than +2 SDS). During rhGH therapy metabolic markers of calcium phosphate metabolism remained largely unchanged; a transient increase in renal phosphate reabsorption and serum phosphate levels were observed and PTH levels slightly increased. No adverse effects were reported.

Discussion: Previous reports on rhGH treatment of short children with primary or metabolic bone diseases (XLH, skeletal dysplasias) have raised concern regarding disproportionate skeletal growth and questioned the benefit of this therapy in advanced age and pubertal stage. We report our preliminary clinical experience with short-term rhGH therapy in two peri-pubertal GH-sufficient short boys with XLH without progression of body disproportion. Long-term controlled studies are warranted to elucidate whether this adjuvant treatment can improve adult height without exacerbating the disproportionate body segments.

Disclosure: The authors declared no competing interests.