PSAT182 Dilemmas in the Diagnosis and Management of Osteoporosis in a patient with Alkaptonuria: Successful Treatment with Teriparatide

INTRODUCTION: Diagnosis and management of osteoporosis in patients with alkaptonuria can be challenging. Coexisting arthritis involving the lumbar spine (LS) and hips can falsely elevate bone density making DXA interpretation difficult. We report a patient with alkaptonuria who was successfully treated with teriparatide in addition to bisphosphonate therapy. CASE HISTORY: A 69-year-old female presented for evaluation of osteoporosis. She was diagnosed with alkaptonuria at age 29 when she reported bilateral conjunctival hyperpigmentation. She was also diagnosed with arthritis requiring left knee joint replacement at the age of 57 years. Subsequently, she underwent left hip, right knee, right hip, and left shoulder joint replacement surgeries. She also sustained fragility fractures in the foot and a 2-inches height loss. Physical examination: normal vital signs. Examination of eyes and ears: bluish black discoloration of the conjunctiva and ear lobes. Heart examination showed normal S1, split S2, and IV/VI systolic murmur over the right parasternal border; the rest of the physical examination revealed limited joint movements of thoracic and lumbar spines, wrists, ankles, knees and hip joints. Laboratory: serum PTH 33 pg./mL, 25-OH vitamins 28 ng/mL, 1,25 (OH)(2) vitamin D 43 pg/mL, osteocalcin 11.6 mg/mL (ref 9.4-47.4), collagen cross-linked C-telopeptide 318 pg/mL (ref 104-1008), tyrosine 79.1 umol/L (ref 31.1-118.1), 24 hours urine homogentisic acid 4.2 gms (ref 20-30 mg). Genetic testing: compound heterozygous mutation for the HGD C. 496T2T>C and HGD C.1102A < G (p.mev368Va) variants, consistent with a diagnosis of alkaptonuria. DXA scan done at the age of 56 years showed osteoporosis (T score -2.7 femoral neck, 1.8 total hip, 2.5 LS). Patient was started on alendronate 70mg PO weekly for 5 years in addition to nitisinone. While on alendronate, she sustained fragility fractures of the right radius and left ankle. After 5 years of alendronate, the patient was transitioned to teriparatide 20-mcg subcutaneously (SC) daily for 2 years followed by annual intravenous zoledronic acid. For the subsequent 7 years, the patient led a healthy, active life with no fractures. Follow-up DXA showed improvement to the osteopenic range at the radius site as degenerative arthritis made interpretation of other sites impossible.This case illustrates the challenges in the diagnosis and treatment of osteoporosis in patients with alkaptonuria. DXA can be ineffective in this condition due to the hip and LS arthritis. Measurement of trabecular bone scoreS and CT of the LS may be better alternate choices. Bisphosphonates alone are typically not effective in preventing fragility fractures in this population but use of teriparatide may be an effective treatment. Further studies are needed to assess the effectiveness of teriparatide in this population but our case shows promise that this treatment result in BMD improvement and fracture prevention. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.