Background: X-linked hypophosphatemia (XLH) are rare inheritable disorders caused by excessive renal phosphate wasting manifesting as rickets in children and osteomalacia in adults. Osteoid accumulates due to the reduced mineralization rate. Based on previous histomorphometric bone biopsy studies it the impression that XLH is a low bone turnover disease. Very little is known about the level of bone markers in XLH and the effects of conventional medical treatment with oral phosphate and alfacalcidol on bone turnover. Sclerostin is a potent inhibitor of bone formation described to be elevated in XLH by Palomo et all, 2014.
Objective and Hypotheses: The aim of this cross-sectional study was to evaluate aspects of bone turnover and sclerostin levels in treated and untreated patients with XLH using biochemical markers.
Method: In 27 XLH adults and in three age and sex matched controls per patient; markers of bone resorption (carboxyterminal cross-linked telopeptide of type 1 collagen, CTX), and formation (N-terminal propeptide of type 1 procollagen, P1NP) in addition to sclerostin were measured. Eleven of the 27 XLH patients had received conventional medical treatment at least six months prior to the examination, 16 were currently untreated.
Results: CTX and P1NP were significantly elevated in XLH, median 810 ng/l [IQR 5001,340] and 90 μg/l , respectively, compared to controls 0.48 μg/l [0.260.71] P<0.001, and 49 μg/l  P<0.001. CTX and P1NP were numerically, but not significantly higher in currently treated XLH 1.24 μg/l [0.582.19] and 136 μg/l , respectively, compared to untreated XLH 0.68 μg/l [0.431.02], P=0.18 and 75 μg/l , P=0.10. Sclerostin was significantly elevated in XLH, median 0.81 ng/ml [0.601.18] vs controls 0.54 ng/ml [0.450.69] P<0.001. There was a trend towards higher sclerostin in untreated 0.83 [0.701.03] compared to treated XLH 0.77 ng/ml [0.581.18] P=0.06.
Conclusion: Both bone resorption and formation markers were significantly elevated in XLH compared to controls indicating a high bone turnover state in XLH. Sclerostin was higher in XLH compared to controls with a tendency towards a lower sclerostin in untreated compared to treated XLH. Thus, even though bone formation was inhibited in XLH as indicated by the elevated sclerostin levels, the overall bone turnover was significantly elevated in XLH tending to be more pronounced in the currently treated. Histomorphometric bone biopsy studies during different treatment regimens are required to further elucidate the effects of treatment on the bone pathology.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology