High Bone Mass From Mutation Of Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6)
Abstract
Wnt/β-catenin signaling is important for skeletal development and health. Eleven heterozygous gain-of-function missense mutations within the first β-propeller of low-density lipoprotein receptor-related protein 5 (LRP5) are known to cause the autosomal dominant disorder called high bone mass (HBM). In 2019, the HBM phenotype was identified in two American families harboring different heterozygous LRP6 missense mutations. We report a 19-year-old Argentinian man referred for "osteopetrosis" and nine years of generalized, medium-intensity bone pain and arthralgias of both knees. His jaw and nasal bridge were broad and several teeth were missing. Routine biochemical testing, including of mineral homeostasis, was normal. Urinary deoxypyridinoline and serum CTX were slightly increased. Radiographic skeletal survey showed diffusely increased radiodensity. DXA revealed substantially elevated BMD Z-scores. Digital orthopantomography confirmed agenesis of his maxillary and mandibular lateral incisors and his second left superior premolar. Cranial magnetic resonance imaging showed diffuse thickening of the calvarium and skull base, dilation of the sheath of the optic nerves containing increased fluid and associated with subtle stenosis of the optic canal, and narrow internal auditory canals. Mutation analyses identified a heterozygous missense mutation in exon 4 of LRP6 leading to a 6-nucleotide/2-amino acid deletion (c.678T>Adel679-684, p.His226Gln-del227-228ProPhe) that would…
How strong is the evidence?
Evidence Hub reads this as a case report, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Erratum to: The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations
- Association between obesity and risk of fracture, bone mineral density and bone quality in adults: A systematic review and meta-analysis
- Dietary Patterns in Relation to Low Bone Mineral Density and Fracture Risk: A Systematic Review and Meta-Analysis
- Association of obesity with bone mineral density and osteoporosis in adults: a systematic review and meta-analysis
- Falls, fractures, and areal bone mineral density in older adults with sarcopenic obesity: A systematic review and meta‐analysis
- Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.