Calcium Deficiency Rickets in African Adolescents: Cortical Bone Histomorphometry

Abstract

Rickets due to dietary calcium deficiency has been well described in black African children, but less is known about this condition in black adolescents. We investigated 26 black adolescents (19 males aged 11 to 19 years and 7 females aged 12 to 15 years) with rachitic leg deformities and 20 controls by routine iliac crest undecalcified cortical bone histomorphometry for disturbances of bone turnover and for mineralization defects, including severity of osteocytic osteolysis (Ot.Olysis) and periosteocytic osteolysis (Peri.Ot.Olysis) of the lacunar‐canalicular space. Serum levels of calcium (sCa), 25‐hydroxyvitamin D (25OHD), 1,25‐dihydroxyvitamin D (1,25(OH) 2 D), and total alkaline phosphatase (ALP) were measured. Histomorphometry showed varying degrees of severity of secondary hyperparathyroidism (2 0 HPT) characterized by hyperosteoidosis, increased erosion, and porosis. Because osteoid was neither being mineralized nor eroded (osteoclasts cannot erode osteoid), it increasingly blocked bone surface needed for osteoclastic resorption. Where osteoid covered >50% of bone surface, osteoid thickness, severity of Ot.Olysis, and extent of Peri.Ot.Olysis increased, sCa and 25OHD declined, and 1,25(OH) 2 D and ALP increased. At 80% osteoid cover, bone remodeling had all but ceased, secondary HPT had changed to osteomalacia, and serum biochemical results had deteriorated further. Disease severity was greater in males than in females, likely because males grow faster and for longer than females. In conclusion, this cross‐sectional clinical case study presents cortical bone histomorphometric data of secondary HPT and its transition to osteomalacia in black adolescents with rickets attributable to dietary calcium deficiency. The bone disease was most severe in older adolescent males. Importantly, bone pathology of calcium deficiency rickets in adolescents was not confined to bone surfaces but also manifested at osteocyte level as Ot.Olysis and Peri.Ot.Olysis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Increased Osteocyte Lacunae Density in the Hypermineralized Bone Matrix of Children with Osteogenesis Imperfecta Type I

“…The positive correlation between the OLS area with osteoid thickness and with mineral apposition rate in trabecular bone may indicate that some osteocytic osteolysis, and thus, some demineralization of the perilacunar matrix, occurs in deeper bone regions, possibly to provide additional calcium to the mineralizing surfaces. In fact, osteocytic osteolysis is observed in metabolic situations of calcium and vitamin D deficiency, which probably also occur transiently during growth [ 69 ].…”

Bone Matrix Mineralization and Response to Burosumab in Adult Patients With X-Linked Hypophosphatemia: Results From the Phase 3, Single-Arm International Trial

“…However, it is well accepted that osteoid seams form an osteoprotective barrier against osteoclasts that do resorb mineralized matrix but can neither attach nor degrade nonmineralized surfaces. (49)(50)(51) Prior to burosumab, osteoid was found to cover nearly 90% of the total trabecular bone surface, which is a fourfold increase compared to normal in young adults, and represents a dramatic restriction of the surface accessible for osteoclastic erosion. (26,28) Because the mineral concentration within the bone matrix increases slowly over years until reaching plateau level, older bone packets "trapped" behind the osteoid surface become gradually more mineralized before being resorbed, mimicking a situation of low bone turnover.…”

“…(8) The origin of these lesions is still unclear but might be related to abnormal periosteocytic matrix remodeling similar as in situations of calcium deficiency. (49,75) It has also been suggested that osteopontin, which accumulates in the XLH bone matrix, particularly within such lesions, impairs mineralization around osteocytes and canaliculi. (9) Recently, similar hypomineralized lesions have also been described in the Hyp mouse, the murine homolog of XLH.…”

Women’s health: optimal nutrition throughout the lifecycle

“…Vitamin A deficiency is also prevalent in adolescent females, but the clinical significance of this deficiency is understudied [ 36 ]. Due to increased requirements and dietary variation, adolescents are also at high risk for calcium deficiency and related bone diseases [ 148 ].…”