Vitamin D Deficiency and Osteoporosis In Hemophilia: An Underappreciated Risk
Authors: Simpson Mindy L. , Valentino Leonard A. 
Published: October 2019

Abstract

Background
Several predisposing risk factors exist for decreased bone mineral density in patients with hemophilia increasing the likelihood of osteopenia and osteoporosis in this population. We report the findings of a study evaluating the association of vitamin D deficiency, osteoporosis and hemophilia.

Objective
Describe the findings of a prospective study evaluating vitamin D levels and bone mineral density in patients with hemophilia. We hypothesize that males with hemophilia have decreased vitamin D levels increasing their risk of osteoporosis along with arthropathy and periods of immobility resulting in reduced bone loading.

Design/Method
Males with hemophilia, age 1-66 years, were eligible for a 3 part study including: 1) data collection on basic health; 2) laboratory measurement of 25-OH Vitamin D, liver enzymes, ionized calcium, magnesium, phosphorus, parathyroid hormone (PTH), and thyroid function tests; and 3) DEXA scan.

Results
86 male subjects, age 2-64 years (mean: 19.9, median: 15.0) including 69 (80%) with hemophilia A and 17 (20%) with hemophilia B were enrolled along with 9 (10%) with history of an inhibitor. Vitamin D levels were reduced in 51 (65%) subjects, including 23 (30%) who were vitamin D insufficient (20-29 ng/mL) and 28 (36%) who were vitamin D deficient (<20 ng/mL). Of the 8 enrolled subjects with history of inhibitor who have had vitamin D levels tested, 7 (88%) are abnormally low with range 17-30 ng/mL for all 8. Among the 61 DEXA scans completed, 8 (13%) were abnormal resulting in a diagnosis of osteoporosis – 6 adults and 2 children (age range 12-56 years). The 2 children with abnormal DEXA scans have a history of inhibitor; the 6 adults are all infected with HIV and/or HCV. 7 of the 8 subjects with osteoporosis had vitamin D levels drawn, where 3 (43%) were abnormally low, with a range of only 10-33 ng/mL among all 7.

Conclusion
Among hemophilia patients enrolled in this study, 65% have abnormally low vitamin D levels which may predispose to decreased bone mineral density over their lifetime. Patients with a history of inhibitor appear to have an increased risk of reduced vitamin D levels. Vitamin D and calcium supplementation may be a simple and inexpensive intervention to address this complication and warrants further investigation in this population. 13% of enrolled subjects had osteoporosis on DEXA where a history of inhibitor or coinfection with HIV and/or HCV is prevalent. High risk subjects may deserve routine screening to allow for earlier intervention.
Funding:CSL Behring Foundation grant

Disclosures:
Valentino: Baxter: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Biogen Idec: Consultancy, Membership on an entity’s Board of Directors or advisory committees; GTC Biotherapeutics: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Inspiration: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity’s Board of Directors or advisory committees.