Effects of Limited Sunlight Exposure on Bone Density in Erythropoietic Protoporphyria
Overview
This cohort study of 139 adult patients with erythropoietic protoporphyria (EPP) found a high prevalence of low bone mineral density (BMD), with 39.5% classified as osteopenic and 15.3% as osteoporotic. Persistent vitamin D deficiency and low body mass index were significant risk factors for low BMD, while cholecalciferol supplementation improved BMD; afamelanotide treatment did not.
Background
Erythropoietic protoporphyria (EPP) is a rare inherited disorder causing painful phototoxic reactions that lead to lifelong avoidance of sunlight and consequent vitamin D deficiency. Vitamin D deficiency is a known risk factor for early-onset osteoporosis. Previous small studies indicated high rates of vitamin D deficiency and low BMD in EPP patients, but longitudinal data and treatment effects on BMD were lacking. Afamelanotide, approved since 2016, reduces phototoxic symptoms and increases sunlight tolerance but its impact on BMD remains unclear.
Data Highlights
Parameter
Value
Number of patients
139
Patients with Z-score < 0 SD at baseline
82.7%
Osteopenia prevalence
39.5%
Osteoporosis prevalence
15.3%
Patients with osteoporosis-related fractures
34.2%
Odds ratio (OR) for low BMD per year of age
1.08 (95% CI 1.03-1.12)
OR for low BMD with persistent vitamin D deficiency
1.11 (95% CI 1.00-1.23)
OR for low BMD per unit BMI
0.91 (95% CI 0.82-0.99)
OR for BMD improvement with vitamin D deficiency
5.51 (95% CI 1.69-17.92)
OR for BMD improvement without cholecalciferol at baseline
0.22 (95% CI 0.04-1.34)
Key Findings
82.7% of EPP patients had a baseline BMD Z-score below 0 SD, indicating widespread low bone density.
Osteopenia was present in 39.5% and osteoporosis in 15.3% of patients, with 34.2% experiencing osteoporosis-related fractures.
Older age, persistent vitamin D deficiency, and lower body mass index significantly increased the odds of low BMD.
Cholecalciferol supplementation was associated with improved BMD, especially in patients with vitamin D deficiency.
Afamelanotide treatment did not demonstrate a significant effect on improving BMD despite increasing sunlight tolerance.
Clinical Implications
Clinicians should monitor bone mineral density and vitamin D status closely in patients with EPP due to their high risk of osteoporosis and fractures. Vitamin D supplementation with cholecalciferol is important to improve and maintain bone health in this population. While afamelanotide improves sunlight tolerance, it does not substitute for vitamin D supplementation in preventing low BMD.
Conclusion
EPP patients exhibit a high prevalence of low bone mineral density primarily driven by vitamin D deficiency and limited sunlight exposure. Lifelong adequate vitamin D supplementation is essential to prevent and improve low BMD in this natural model of sunlight avoidance.
References
Erasmus MC Study 2023 -- Effects of Limited Sunlight Exposure on Bone Density in Erythropoietic Protoporphyria
