Low Bone Mineral Density Presenting as Bone Pain Due to Gilbertʼs Syndrome

Abstract

Gilbert's Syndrome (GS) is a deficiency of uridine diphosphate glucuronosyltransferase leading to mild levels of impaired hepatic clearance and the buildup of unconjugated bilirubin (UB). Hepatic osteodystrophy has not yet been defined in GS. We describe two cases of GS associated with low bone mineral density (BMD) presenting as bone pain. 35 year-old Hispanic Air Force male with a one year history of simultaneous polyarthropathy, abdominal bloating, constipation, unintentional twenty pound weight loss and a transient episode of jaundice that self-resolved. He was evaluated by gastroenterology, hepatology, rheumatology, endocrinology and infectious disease. During his workup he was found to have an elevated indirect bilirubin consistent with GS. He had mildly elevated transaminase levels with negative hepatitis serologies, fibroscan and liver biopsy with no evidence of fibrosis. Ceruloplasmin, copper, AP, GGT, A-1-AT, calcitonin, PTH, telopeptide, calcium, vitamin D, cortisol and hormone levels were normal. A DEXA scan revealed low BMD with a Z-score of -2.3. Workup for celiac, IBD, connective tissue diseases, mastocytosis and infectious etiologies were negative. He was diagnosed with ROME III IBS, GS and borderline OP. 56 year-old Caucasian Navy male with a ten year history of polyarthropathy, fatigue, weakness, transient skin rashes and unintentional weight loss. Serological and imaging studies were unremarkable for primary arthropathies. He was found to have elevated UB consistent with GS and an elevated tTG IgA. He was placed on a high gluten diet and his symptoms clinically worsened. A CT and EGD with biopsy confirmed the diagnosis of celiac disease. His vitamin, calcium, cortisol and hormone studies were normal. A DEXA revealed low BMD and a T-score of -2.7 consistent with OP. He has initiated treatment with a bisphosphonate. GS is characterized by fluctuating UB often with fasting or illness. Due to the benign nature of the disease, currently no treatment is required. In vitro studies have shown UB to inhibit osteoblastic proliferative activity. A retrospective pilot study showed a significant negative correlation between BMD and UB in patients with GS. This case series illustrates bone pain in two men with low BMD in GS not described before. GS plays a role in bone homeostasis and elevated UB appears to contribute to the severity and risk of OP. There is a future role for earlier detection, treatment and potential for normalizing bilirubin.1322_A.tif Figure 1: Normal MRI of the liver1322_B.tif Figure 2: BMD measured at the lumbar spine is 0.922 gm/cm2 with a Z-score of -2.3.1322_C.tif Figure 3: BMD measured at the lumbar spine is 0.903 gm/cm2 with a T-score of -2.7 and a Z-score of -1.9.