Escape from Denosumab Mediated Suppression of Bone Resorption in Primary Biliary Cirrhosis

Presentation Number: SAT 322
Date of Presentation: April 1st, 2017

Tarunya Reddy Vedere*1 and Faryal Sardar Mirza2
1University of Connecticut, Farmington, CT, 2University of Connecticut Health Center, Farmington, CT

Abstract

Introduction:

The incidence of osteoporosis (OP) in primary biliary cirrhosis (PBC) ranges from 20 to 44% and increases with disease progression(1). An increase in bone resorption and slowed remodeling are thought to contribute to the low bone mineral density (BMD). There is no reported data on the use of denosumab for OP in patients with PBC.

Clinical case:

A 68-year-old female with a history of PBC, scleroderma, Raynaud’s disease, hypothyroidism and OP was referred for declining bone density while on a drug holiday for 2 years, after completing 5 years of treatment with alendronate. History was significant for 3 inches of height loss and a moderate wedge compression fracture in the thoracic spine noted on vertebral morphometric analysis at presentation. Risk factors for OP included being postmenopausal with history of early menopause (42 years), Caucasian race, chronic liver disease, prior cigarette smoking and family history of OP. She was never on long-term steroids. BMD by DEXA showed OP in the spine (L1-L2 T-score of -2.7; BMD 0.937 g/cm2) and forearm (33% radius T score of -2.8) and osteopenia at the hips. Bone turnover markers were elevated with Bone Specific Alkaline Phosphatase (BSAP) of 50.8 IU/L (7-22 IU/L) and urine N-terminal telopeptide (NTX) of 98 NTX units (26-124 BCE/mm creatinine), with normal calcium and Vitamin D levels. It was decided to start her on denosumab. Due to high bone turnover at baseline, markers were repeated at 6 and 12 months. Her urine NTX was only 17% and 22% suppressed at 6 and 12 months respectively after starting denosumab. BSAP remained above the upper limits of reference range. BMD was stable with non-significant increase at 1 year. A nuclear bone scan done to rule out metastatic disease did not show any focal uptake. Hence denosumab was continued every 6 months and her treatment period was uneventful except for a wrist fracture sustained in the 3rdyear of treatment.

To investigate if denosumab was indeed suppressing bone resorption, urine NTX levels were checked 1, 3 and 6 months after the 5thinjection. Urine NTX was 72% suppressed at 1 month and only 22% suppressed at 3 months. DEXA scan after 3 years of treatment with denosumab did show a significant increase in BMD at lumbar spine of 9.1% (T-score of -2 at L1-L2) and stable BMD at the hips.

Conclusion:

Our patient demonstrated escape from suppression of bone resorption effects of denosumab. Prior studies have shown that denosumab given every 6 months causes sustained suppression of bone resorption with a nadir at 1 month and sustained suppression at 3 and 6 months(2). Escape from suppression of bone resorption with denosumab has been reported in patients with advanced cancer and bone metastases but not in OP(3). The effect of denosumab was much more short lived in our patient despite a positive effect on bone density. This case highlights the need to be vigilant in monitoring the effect of treatment with denosumab in patients with PBC.

 

Nothing to Disclose: TRV, FSM