Dysosteosclerosis presents as an “Osteoclast-Poor” form of osteopetrosis: Comprehensive investigation of a 3-year-old girl and literature review

Abstract

Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to –2.3 SD. Head circumference was +4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology. © 2010 American Society for Bone and Mineral Research.

Relationship between plasma osteocalcin, glycaemic control and components of metabolic syndrome in adult Nigerians with type 2 diabetes mellitus

“…Type 2 DM is a metabolic disorder associated with chronic hyperglycaemia and characterized by insulin resistance and relative insulin deficiency. In this study, the finding of significantly lower levels of plasma osteocalcin in patients with type 2 DM when compared to the nondiabetics is in line with reports from China [15], South Korea [16] and Sweden [17]. A number of mechanisms may be involved in these findings.…”

“…The inverse relationship observed between fasting plasma glucose and osteocalcin from most previous studies [15,17,26] was also significant in this study. In some studies the uncarboxylated form of osteocalcin appeared to mediate the effects of osteocalcin on metabolic phenotype [22,27].…”

Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders

“…Although a slight serum LDH elevation of 611 IU/L (normal 300 to 600 IU/L) was observed in Kenney-Caffey disease (n ¼ 1), levels otherwise were normal in the remaining 40 Shriners patients representing progressive osseous heteroplasia (19) (2), Lenz-Majewski syndrome (1), dysosteosclerosis (20) (1), bisphosphonate-induced osteopetrosis (8,18) (2), osteopathia striata with cranial sclerosis (1), polycystic osteosclerosis with hypercalcemia (21) (1), Camurati-Engelmann disease (1), osteopoikilosis including Buschke-Ollendorff syn- , bowing, and pseudofractures (short arrow) present also in the posterior ribs and every extremity long bone (C). There was vertebral body endplate sclerosis, anterior compression fractures of the lower thoracic and upper lumbar spine, and spondylolysis in keeping with OPT (8) (arrow) (D).…”

Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

“…A sustained level of low alkaline phosphatase is seen in HPP, dysosteosclerosis, cleidocranial dysplasia, Mseleni joint disease, and benign familial hypophosphatasemia. Dysosteosclerosis, a form of osteopetrosis with a gene mutation localized to SLC29A3, is characterized by short stature, fractures, cranial nerve palsy, delayed developmental milestones, and failure of tooth eruption [96]. Cleidocranial dysplasia, due to a RUNX2 mutation, is associated with abnormal clavicles, short ribs, patent sutures and fontanelles, supernumerary teeth, short stature, and brachydactyly [97].…”