Dysosteosclerosis presents as an “Osteoclast-Poor” form of osteopetrosis: Comprehensive investigation of a 3-year-old girl and literature review
Open accessAbstract
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.
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Active bone formation is lacking in osteoclast-poor osteopetrosis due to TNFRSF11A mutations or in dysosteosclerosis.
“In contrast to “osteoclast-rich” OPT, active bone formation is lacking in “osteoclast-poor” OPT (due to TNFRSF11A mutations226) or dysosteosclerosis (DSS) (an OPT of unknown etiology227).”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [227]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
- Authors
- Whyte, M. P., Wenkert, D., McAlister, W. H., Novack, D. V., Nenninger, A. R., Zhang, X., Huskey, M., & Mumm, S.
- Affiliations
- Barnes-Jewish Hospital (US)
- Shriners Hospitals for Children - St. Louis (US)
- St. Louis Children's Hospital (US)
- Corresponding author
- Whyte, Michael P
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-05-17
- Volume
- 25
- Issue
- 11
- Pages
- 2527-2539
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC3179286
- OpenAlex
- W2086961812
- Cited by
- 43
- References
- 52
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 6 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Foundation for Barnes-Jewish Hospital
- Shriners Hospitals for Children
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067145)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- osteopetrosis, primary spongiosa, short stature, bone histology, bone turnover markers, parathyroid hormone, genetic etiology, pediatric bone disease
- MeSH terms
- Adult, Bone and Bones, Child, Preschool, Diagnosis, Differential, DNA Mutational Analysis, Family, Female, Humans, Infant, Infant, Newborn, Osteoclasts, Osteopetrosis, Osteosclerosis, Pregnancy, Radiography, Thoracic, Tomography, X-Ray Computed
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