Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients.
Abstract PTH is only one measurable index of skeletal health and we reasoned, that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-[OH]-D level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency would therefore be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters including osteoid indices were quantified using the Osteomeasure system according to ASBMR standards and serum 25-[OH]-D levels were measured for all patients. Statistical analysis was performed by student's t-test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, i.e. a pathologic increase in osteoid. Indeed 36.15% of the analyzed patients presented with an OS/BS of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in OV/BV greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of BV/TV, throughout all ages and affected both sexes equally. While we could not establish a minimum 25-[OH]-D level that was inevitably associated with mineralization defects we did not find pathologic accumulation of osteoid in any patient with circulating 25-[OH]-D above 75nmol/l. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25-[OH]-D below 75nmol/l and strongly argue that in conjunction with a sufficient calcium intake the dose of vitamin D supplementation should ensure that circulating levels of 25-[OH]-D reach this minimum threshold (75nmol/l or 30ng/ml) to maintain skeletal health.
Abstract PTH is only one measurable index of skeletal health and we reasoned, that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-[OH]-D level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency would therefore be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters including osteoid indices were quantified using the Osteomeasure system according to ASBMR standards and serum 25-[OH]-D levels were measured for all patients. Statistical analysis was performed by student's t-test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, i.e. a pathologic increase in osteoid. Indeed 36.15% of the analyzed patients presented with an OS/BS of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in OV/BV greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of BV/TV, throughout all ages and affected both sexes equally. While we could not establish a minimum 25-[OH]-D level that was inevitably associated with mineralization defects we did not find pathologic accumulation of osteoid in any patient with circulating 25-[OH]-D above 75nmol/l. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25-[OH]-D below 75nmol/l and strongly argue that in conjunction with a sufficient calcium intake the dose of vitamin D supplementation should ensure that circulating levels of 25-[OH]-D reach this minimum threshold (75nmol/l or 30ng/ml) to maintain skeletal health.