Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH).

X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized. We analyzed transiliac bone biopsies from four adult patients, two of them severely affected due to no diagnosis and no treatment until adulthood. We used light microscopy, qBEI and FTIRI to study histology, histomorphometry, bone mineralization density distribution, properties of the organic matrix and size of hypomineralized periosteocytic lesions. Non-treatment resulted in severe osteomalacia, twice the amount of mineralized trabecular volume, multiple osteon-like perforations, continuity of lamellae from mineralized to unmineralized areas and distinctive patches of woven bone. Periosteocytic lesions were larger than in treated patients. The latter had nearly normal osteoid thicknesses, although surface was still elevated. The median calcium content of the matrix was always within normal range, although the percentage of lowly mineralized bone areas was highly increased in non-treated patients, resulting in a marked heterogeneity in mineralization. Divalent collagen cross-links were evident independently of the mineral content of the matrix. Broad osteoid seams lacked measurable pyridinoline, a mature trivalent cross-link and exhibited considerable acidic lipid content, typically found in matrix vesicles. Based on our results, we propose a model that possibly integrates the relationship between the observed mineralization disturbances, FGF23 secretion and the known osteopontin accumulation in XLH.

Eplerenone in patients with chronic recurring central serous chorioretinopathy.

PURPOSE: To evaluate the effect of eplerenone on patients with long-term recurring central serous chorioretinopathy (CSC). METHODS: In this retrospective case series, 11 patients with chronic recurring CSC were included. The main focus was to include patients who had undergone photodynamic therapy (4 patients), had undergone anti-vascular endothelial growth factor treatment (3 patients), or had several episodes of CSC in the past (4 patients) (mean age 60 years; SD 9.7, range 47-76). RESULTS: Four patients (36.4%) had full resorption of neurosensory detachment under therapy of eplerenone with improvement of vision, while 4 more patients had improvement of vision despite residual edema. Eight patients (73%) had improved visual acuity (VA) at the end of eplerenone therapy, 2 patients had no change in VA, and 1 patient decreased VA. Mean time of treatment was 10.6 ± 9.9 weeks (range 3-38 weeks). All patients showed subretinal deposits, with 6 of them having hyperautofluorescent subretinal deposits. CONCLUSIONS: Eplerenone represents a new treatment option for patients with CSC. Our data indicate a good response in those patients, leading to improvement of VA in 73% of patients.