ESPE Abstracts

Introduction: Primary osteoporosis are frequently linked to syndromic conditions such as osteogenesis imperfecta which also involves extra esqueletic tissues. With the advancement of medicine, this group has been reduced, due the ability to specifying the causal pathogenic variants. Among these, the LRP5 (Low-density lipoprotein receptor-related protein 5) gene mutations are the most frequent cause. LPR5 is a fundamental coreceptor in the wnt/betacatenin signaling pathway, which is the main metabolic pathway of osteoblasts, the mutations of this one, result in decreased bone formation and could be one of the main causes of primary osteoporosis.

Case report: Case Nº1: A 12-year-old boy, previously healthy, evaluated for chronic knees and back pain. Not medical history of bone disease, no familiar history of osteoporosis. Physical exam with out blue esclera, no dismorfic features, not enamel tooth alterations or other extraesqueletic findings.

Laboratory: Serum Calcium 2.35 mmol/l, phosphemia 1.42 mmol/l, albumin 4.5 g/dl, FA: 172 U/L, PTH 5.3 pmol/l (normal value <6.89), 25OH vitamin D 16.7 mg/dl, TSH 1.98 IU/L, FT4 1.4 ng/dl, negative hypercalciuria, negative anti-transglutaminase antibodies and nugent test. Chest X-ray showed diffuse osteopenia, vertebral fracture in T6-T9 Bone mineral densitometry of lumbar spine: 0.136 gr/cm3, Z score: -5.0 Genetic study shows a variant of uncertain significance in LPR5 gene c.1021G> A; pGlu341Lys. When is classified in varsome, it could be reclassified as probably pathogenic if correspond a de novo variant.

Case Nº2: 12-year-old boy, evaluated for a history of 1 year of lumbar pain, x-ray of spine showed a fracture in vertebral bodies from D 12 to L3. No personal or family history of bone mineral disease, no history of bone fractures. Physical exam: No abnormal findings. Laboratory: Calcium: 2.15 mmol/l, phosphemia 1.23 mmol/l, albumin 4.0 g/dl, FA 246 U/L, PTH 2.6 ng/dl normal value <6.89), 25OH vitaminD 51 mg/dl, TSH 1.87 IU/L, T4 9.3 ng/dl, negative hypercalciuria, negative anti-transglutaminase antibodies. Lumbar spine volumetric bone density of 0.205 gr/cm3 and Z score -2.7 DS. Genetic study results in a variant of uncertain significance in LPR5, c.1696C> T; p.Arg566Cys. Again, reclassified in varsome, it could be pathogenic, if parentes do not have the mutation.

Discussion/Conclusion: LRP5 gene mutations have been reported as one of the main causes of primary osteoporosis. There are 2 phenotypes due to loss of protein function, early-onset osteoporosis autosomal dominant, and the osteoporosis-pseudoglioma syndrome autosomal recessive.