Bone Abstracts

Background: Osteogenesis imperfecta (OI) due to FKBP10 mutation is a rare variant of OI. FKBP10 encodes for FKBP65, a molecular chaperon that interacts with type I procollagen to prevent premature fibril formation and plays a role in collagen crosslinking. Defects in FKBP65 result in a spectrum of moderate to severe OI with remarkable variability in phenotypes.

Presenting problem: The patient is the first child of non-consanguineous Caucasian parents. She presented with multiple long bone and rib fractures, as well as Wormian bones shortly after birth, consistent with the clinical diagnosis of OI. Bisphosphonate treatment was started at the age of 6 weeks. Molecular studies including testing for COL1A1, COL1A2, CRTAP and LEPRE1 were negative in the early assessment. While receiving regular Pamidronate infusions, she continued to fracture with a total of 24 mainly long bone fractures by the age of 4 years. She showed no deformities or contractures. She started walking at the age of 22 months, other developmental milestones were appropriate. Skin biopsy showed normal collagen formation. Pamidronate treatment was stopped after 4 years. Further genetic testing confirmed a compound heterozygous mutation in the FKBP10 gene c.[310C>T];[944_972del]. 1 year after stopping Pamidronate treatment, her BMD z-score (L1-L4) was +2.2, however she continued to fracture and experience bone pain.

Clinical management: She was started on Zoledronate at the age of 6 years. Bone biopsy prior to Zoledronate showed increase in bone turnover. Symptoms did not improve on Zoledronate and treatment was stopped again after 1 year with a BMD z-score of +2.7 (L1-L4). Repeat bone biopsy at age 9 years indicated low bone turnover. Additional HRpQCT imaging showed a non-homogenous and trabecuralized cortex, abnormalities in the trabecular struts and rods and periosteal reaction including periosteal fissure with poor mineralization.

Discussion: We present a 9 year old female with severe non-deforming OI due to a compound heterozygous FKBP10 mutation non-responsive to bisphosphonate treatment. Her recent bone biopsy indicates low bone turnover. BMD Z-score and HRpQCT results indicates qualitative rather than quantitative bone impairment. Further medical therapy with an anabolic agent such as growth hormone or possibly PTH is under consideration.

Disclosure: The authors declared no competing interests.