It is generally accepted that the spine is the site of predilection for retinoid-induced skeletal abnormalities. However, the reported prevalence of skeletal problems varies widely. To investigate the frequency and severity of retinoid-induced spinal abnormalities, all records of patients who underwent spinal radiographs at the request of the department of dermatology between 1983 and 1993 were reviewed. This group of 135 patients comprised the total population of retinoid-treated patients and those patients who were investigated for possible future retinoid treatment. The mean treatment period in the total group was 30 months and the mean cumulative dose of retinoid was 31 g. In 50 patients the treatment period was > or = 24 months with 30 patients being treated for more than 48 months. Baseline radiographs were available from 26 patients and these were compared with the most recent X-rays during treatment. The mean treatment period in this 'prospective group' was 25 months and the mean cumulative dose of retinoid was 25 g. The prevalence of diffuse idiopathic skeletal hyperostosis (DISH), degenerative changes and osteoporosis in the total group was respectively 16%, 53% and 29%. There was no statistically significant relation between the duration of treatment or the cumulative dose and the prevalence or severity of DISH, degenerative changes and osteoporosis. Only the age of the patients was significantly related to the frequency and severity of skeletal abnormalities. In the 'prospective group', again, no important changes were observed between the radiographs at baseline and during treatment. In this study no relation whatsoever between spinal abnormalities and prolonged oral retinoid treatment could be established. The performance of annual routine spinal radiographs during retinoid treatment is not necessary in our opinion. Additional controlled and prospective studies on spinal and extraspinal skeletal abnormalities are required to develop definitive screening guidelines for patients submitted to long-term retinoid treatment.

/pdf/prolonged-treatment-with-oral-retinoids-in-adults-no-n4zauju4db.pdf

Prolonged treatment with oral retinoids in adults : no influence on the frequency and severity of spinal abnormalities

Background. 13-Cis-retinoic acid has an influence on bone in patients on long-term treatment as well as on short-term treatment. The presence of skeletal abnormalities after the treatment was established by roentgenologic and scintigraphic examinations. We wanted to know whether a 6-month course of low-dose 13-cis-retinoic acid has a clinically important influence on bone density in men with severe acne.



Methods. We examined 15 men with severe acne before and after treatment with 13-cis-retinoic acid by dual-photon absorptiometry of the lumbar spine.



Results. The mean increase in bone density was 3.0% (95% confidence interval 1.3–4.5), which is normal for the period from puberty to late twenties. Bone density increased in 13 of our 15 patients.



Conclusions. As shown by this highly sensitive modern densitometric method, 13-cis-retinoic acid has no clinically important influence on bone density in male patients with severe acne.

13-cis-retinoic acid and bone density

Prolonged treatment with oral retinoids in adults: no influence on the frequency and severity of spinal abnormalities

Der Einsatz von Vitamin A und seinen Derivaten in der Dermatologie hat trotz uber 30jahriger erfolgreicher Retinoidforschung nicht an Aktualitat verloren. Die bisherige Forschung hat ein weites Wirkspektrum der Retinoide aufgezeigt, wie Einflus auf Zellproliferation, Zelldifferenzierung, Keratinisierung, Sebumproduktion, Reparatur der durch Sonnenlicht geschadigten Haut, Entzundungshemmung, Immunmodulation oder Pravention und Therapie von Prakanzerosen und einigen spezifischen Malignomen. Wahrend die Retinoide in der Behandlung von dermatologischen Krankheitsbildern wie Krankheiten der Talgdrusen und Haarfollikel, insbesondere der Akne conglobata, Psoriasis sowie kongenitalen und erworbenen Verhornungsstorungen bereits fest etabliert sind, steckt die klinische Anwendung der Retinoide in der Onkologie sowie bei verschiedenen immunologischen Krankheitsbildern noch in den Kinderschuhen. Bei Erkrankungen der Talgdrusen ist lediglich das systemisch verabreichte Isotretinoin erfolgreich einsetzbar. In der Behandlung der Psoriasis und anderen keratinisierenden Dermatosen ist Etretinat aufgrund seiner besseren Wirk- und Nebenwirkungsprofils im Vergleich zum Isotretinoin das Mittel der Wahl. Bei Patientinnen, bei denen in nicht zu ferner Zukunft eine Schwangerschaft erwagt wird, ist Isotretinoin wegen seiner kurzeren Eliminationshalbwertszeit dem Etretinat vorzuziehen. Bei Prakanzerosen werden Retinoide sowohl topisch als auch systemisch appliziert.

Nutzen und Risiken der Retinoid-Therapie

Bone and ligament lesions induced by systemic retinoids (premature epiphyseal closure, osteophytes, calcification of ligaments, osteoporosis, etc.) are radiologically nonspecific. We assessed the incidence of "possibly retinoid-induced bone and ligament lesions" (MRKBV) in 46 patients (aged 24-82 years) who had been treated with various systemic retinoids for a variety of chronic dermatoses for an average of 4.5 years and compared the data with observations in a similarly structured group of control patients. All types of MRKBV were found more frequently in the retinoid group (41.3% vs 30.2%) and were more severe. Differences were only slight, however, being statistically significant only for moderate and severe MRKBV and for calcification of ligaments. Within the retinoid group, MRKBV were strikingly correlated with age, whereas no correlation was found with duration of treatment, mean daily and cumulative retinoid dose, underlying dermatosis, type of retinoid used or presence of other retinoid side-effects. Within the control group, MRKBV were also correlated with age, although to a lesser degree. We conclude that retinoids amplify and accelerate physiological and pathophysiological remodelling of the bones, thereby producing a varied range of lesions, which are characteristic for the age and the individual constitution of the patient treated. Retinoid-induced bone and ligament lesions, as a rule, do not cause subjective symptoms and are not associated with predictive or accompanying laboratory values. Also, MRKBV are not paralleled by other retinoid-induced side-effects (hyperlipidaemia, elevation of liver transaminases). In 16 cases in which bone X-ray had been performed prior to retinoid treatment, no indication of reversibility of MRKBV was found.(ABSTRACT TRUNCATED AT 250 WORDS)

[Retinoid-induced changes of the bones and ligaments].

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[Retinoid-induced changes of the bones and ligaments].