Does long-term therapy with acitretin cause osteoporosis?/nA 65-year-old man with psoriasis and pso

Fråga: Does long-term therapy with acitretin cause osteoporosis? A 65-year-old man with psoriasis and psoriatic arthropathy has been treated with acitretin (Neotigason) for approximately 15 years. During a hip arthroplasty, the orthopedian noticed that the bone appeared to be soft.

Sammanfattning: There are reports of an association between the use of retinoids and skeletal changes, including osteoporosis. Case reports dominate the literature in this field, but a few small, cross-sectional studies with some design problems have been conducted and there is no clear-cut conclusion to be drawn.

Svar: A high dietary intake of vitamin A has been associated with skeletal changes including osteoporosis in case reports and epidemiological studies. However, a causal relationship has not been verified (1). Rats fed high doses of retinyl esters exhibit spontaneous fractures. Retinoic acid has been shown to inhibit osteoblast activity and stimulate osteoclast formation in vitro. Retinoid receptors are found in osteoblasts and osteoclasts. Another proposed mechanism of retinoids interfering with bone mineralization is antagonism of the vitamin D receptor (1).

Acitretin is the active metabolite of etretinate. They are both retinoids that have been used for the treatment of disorders of keratinisation. Etretinate is no longer in clinical use (2). They have both been associated with skeletal abnormalities such as spinal hyperostoses, calcification of tendons and ligaments, and osteoporosis (2,3,4,5,6). No properly controlled studies have been conducted to elucidate this association and the studies that have been conducted have given conflicting results.

To narrow down to the specific question of retinoids and osteoporosis, there have been two studies on etretinate showing a statistically significant lower bone mass density (BMD) in treated patients compared to the age-matched population mean (7,8). The differences were around 10-15%. On the other hand, a similar study with acitretin was unable to show that either duration of treatment or cumulative dose was a risk factor for bone loss in acitretin-treated patients (2).

All three studies were small (13-30 patients), cross-sectional and not properly controlled. The association in the etretinate studies may well be confounding by indication as disorders of keratinisation per se might be associated with osteopenia or osteoporosis (e.g. 9). The negative finding in reference 2, might on the other hand be due to differences in study design compared to references 7 and 8: bone densiometry was used to classify patients into a normal and a bone loss group rather than evaluated in a quantitative way. On the other hand the use of WHO criteria for osteopenia and osteoporosis in reference 2 might have a greater clinical significance, than the numbers reported in references 7 and 8.