Bone phenotype of patients with genetic forms of lipodystrophy: a systematic review of literature.

Abstract

Objective: Congenital lipodystrophies (LDs), including congenital generalized LD (CGL) and familial partial LD (FPLD), are rare disorders characterized by absent or abnormal adipose tissue distribution, leading to clinical, hormonal, and metabolic complications. Although these systemic features are well described, data on bone involvement are limited. This literature review summarizes current evidence on bone manifestations in genetic LDs and potential underlying mechanisms.

Methods: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library using terms related to LD and bone outcomes. No restrictions on date, language, or study design were applied. Studies reporting bone-related outcomes in genetic LD in humans were included. Study quality was assessed using PRISMA guidelines and the JBI checklist.

Results: Of 2632 studies identified, 15 met the inclusion criteria. Most focused on CGL1 and CGL2; no studies were found on CGL3 or CGL4. Reported bone abnormalities in CGL1 and CGL2 included osteolytic lesions, bone cysts, osteosclerosis, and pseudo-osteopoikilosis, predominantly in long bones. Bone mineral density (BMD) was generally normal to high at trabecular sites. In contrast, FPLD2 was characterized by reduced BMD at cortical sites and lower trabecular bone score, suggesting impaired bone quality. Proposed mechanisms include reduced bone marrow adipose tissue, disrupted marrow fat conversion, and altered endocrine signaling.

Conclusion: Bone abnormalities are characteristic yet often underrecognized features of genetic LDs, particularly CGL1 and CGL2. Current evidence underlines the broad skeletal impact of adipose dysfunction and highlights the need for standardized, genetically stratified studies to clarify bone risk and guide clinical management in congenital LD.