Related Experiment Videos
Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a correlative clinical-histomorphometric
D Gazit1, M Tieder, U A Liberman
1Division of Oral Pathology and Bone Laboratory, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
Insights
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) causes osteomalacia due to hypophosphatemia alone. Elevated 1,25-dihydroxyvitamin D reflects phosphate wasting, not bone disease pathogenesis.
Area of Science:
- Pediatric Endocrinology
- Bone Metabolism
- Mineralization Disorders
Background:
- Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder.
- Understanding the bone pathology and pathogenesis of HHRH is crucial for effective treatment.
Purpose of the Study:
- To characterize the bone disease in HHRH patients.
- To investigate the relationship between serum phosphorus, 1,25-dihydroxyvitamin D, and bone mineralization.
- To determine the role of hypophosphatemia and vitamin D in HHRH pathogenesis.
Main Methods:
- Transilial bone biopsy analysis in HHRH patients and asymptomatic hypercalciuric subjects.
- Histomorphometric analysis of bone mineralization, osteoid surface, and seam width.
- Correlation analysis between serum phosphorus, 1,25-dihydroxyvitamin D, alkaline phosphatase, and bone parameters.
Main Results:
- HHRH patients exhibit clear signs of osteomalacia, including irregular mineralization fronts and elevated osteoid parameters.
- A strong inverse correlation exists between serum phosphorus and osteoid parameters.
- Elevated serum 1,25-dihydroxyvitamin D levels in HHRH correlate positively with osteoid parameters and mineralization lag time.
Conclusions:
- Hypophosphatemia alone is sufficient to cause osteomalacia in HHRH.
- Elevated 1,25-dihydroxyvitamin D in HHRH reflects the renal phosphate leak severity but does not contribute to bone disease pathogenesis.
- Phosphate therapy leads to remission of bone disease in HHRH.
Abstract:
We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface. Parametric and nonparametric statistical analyses performed on a pooled sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and correlated positively with osteoid parameters and the mineralization lag time. Serum alkaline phosphatase showed similar relationships. These results as well as the clinical, biochemical, and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D reflects the degree of the primary renal phosphate leak, but is not involved in the pathogenesis of the bone disease.