tretinoin and Spinal-Diseases

The repeating pattern of the human vertebral column is shaped early in development, by a process called somitogenesis. In this embryonic process, pairs of mesodermal segments called somites are serially laid down along the developing neural tube. Somitogenesis is an iterative process, repeating at regular time intervals until the last somite is formed. This process lays down the vertebrate body axis from head to tail, making for a progression of developmental steps along the rostral-caudal axis. In this review, the roles of the Notch, Wnt, fibroblast growth factor, retinoic acid and other pathways are described during the following key steps in somitogenesis: formation of the presomitic mesoderm (PSM) and establishment of molecular gradients; prepatterning of the PSM by molecular oscillators; patterning of rostral-caudal polarity within the somite; formation of somite borders; and maturation and resegmentation of somites to form musculoskeletal tissues. Disruption of somitogenesis can lead to severe vertebral birth defects such as spondylocostal dysostosis (SCD). Genetic studies in the mouse have been instrumental in finding mutations in this disorder, and ongoing mouse studies should provide functional insights and additional candidate genes to help in efforts to identify genes causing human spinal birth defects.

Topics: Animals; Biological Clocks; Body Patterning; Dysostoses; Embryonic Development; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Humans; Mice; Receptors, Notch; Signal Transduction; Somites; Spinal Diseases; Spine; Tretinoin; Wnt Proteins

The segmented body plan of vertebrates is established during somitogenesis, a well-studied process in model organisms; however, the details of this process in humans remain largely unknown owing to ethical and technical limitations. Despite recent advances with pluripotent stem cell-based approaches

Topics: Body Patterning; Cell Culture Techniques, Three Dimensional; Extracellular Matrix; Fibroblast Growth Factors; Humans; In Vitro Techniques; Induced Pluripotent Stem Cells; Models, Biological; Mutation; Somites; Spinal Diseases; Tretinoin; Wnt Signaling Pathway

To observe the morphological features of the lumbosacral neural tube defects (NTDs) induced by all-trans retinoic acid (atRA) and to explore the pathogenesis of these defects.. Rat embryos with lumbosacral NTDs were obtained by treating pregnant rats with administration of atRA. Rat embryos were obtained by cesarean. Fetuses were sectioned and stained with hematoxylin-eosin (H&E). Relevant structures including caudal neural tube were examined. In the atRA-treated rats, about 48% embryos showed lumbosacral NTDs. There appeared a dorsally and rostrally situated, neural-plate-like structure (myeloschisis) and a ventrally and caudally located cell mass containing multiple canals (hamartoma) in the lumbosacral NTDs induced by atRA.. Retinoic acid could disturb the notochord and tail bud development in the process of primary and secondary neurulation in rat embryos, which cause lumbosacral NTDs including myeloschisis and hamartoma. The morphology is very similar to that happens in humans.

Topics: Abnormalities, Drug-Induced; Animals; Embryonic Development; Female; Gestational Age; Hamartoma; Keratolytic Agents; Neural Tube Defects; Notochord; Pregnancy; Rats; Rats, Wistar; Spinal Cord; Spinal Diseases; Spine; Teratogens; Tretinoin

We prospectively analyzed skeletal changes of 16 patients who were treated with acitretin for various disorders of keratinization at doses of 10-50 mg/day (overall mean 0.4 mg/kg/day) for 7-12 months (mean 11.4 months). Skeletal changes from pretherapy findings were observed in 5 patients. In 4 of 5 patients they appeared to be linked to a preexisting degenerative pathology and could not be attributed to acitretin therapy. However, in 1 patient a spinal osseous side effect could not be excluded. No retinoid-induced extraspinal tendon or ligament calcifications were observed.

Topics: Acitretin; Adolescent; Bone and Bones; Bone Diseases; Female; Humans; Male; Middle Aged; Prospective Studies; Skin Diseases; Spinal Diseases; Tretinoin

We evaluated the effects of long- and short-term isotretinoin therapy on the skeletons of patients. Eight patients who were treated with isotretinoin for disorders of keratinization received frequent radiographic evaluations for 4 to 9 years. Seven patients developed multiple hyperostoses at the spine and extremities. Hyperostoses increased in size and number over the course of therapy, although relatively few sites were symptomatic. Hyperostoses typically developed first in the spine and later in the extremities, where both bilaterally symmetric and asymmetric involvement was observed. After 5 years of therapy one patient did not develop hyperostosis. In a group of nine patients who received a relatively high dose of isotretinoin in 1982 for the treatment of acne, two patients developed tiny, asymptomatic hyperostoses. One patient had hyperostoses 1 year after isotretinoin therapy, which remained unchanged 3 years later, whereas the other patient had one hyperostosis 4 years after therapy had been stopped. Although we suspect that these hyperostoses were retinoid induced, they should not be of concern for the patient needing routine isotretinoin therapy for the treatment of cystic acne.

Topics: Acne Vulgaris; Adolescent; Adult; Bone Diseases; Child; Female; Follow-Up Studies; Humans; Ichthyosis; Isomerism; Isotretinoin; Male; Radiography; Skin Diseases; Spinal Diseases; Time Factors; Tretinoin

Skeletal effects of retinoids on the spine were studied in two clinical trials. In the first study, spinal radiographs of 96 patients who had been treated with isotretinoin for 4 to 9 months were reviewed. The average age of these patients was 25 years, and during treatment or within 2 1/2 years after the end of treatment, 26% of the patients showed progressive formation of small bony spurs consisting of tiny horizontal excrescences that arose at the anterior margin of one or more vertebral bodies adjacent to the intervertebral disk. In a second study, the radiographs of 241 patients with psoriasis who were treated continually for 1 to 2 years with acitretin were examined. Many of these patients had abnormal radiographs at the start of therapy. These preexisting conditions included psoriatic arthritis, degenerative arthritis, and diffuse idiopathic skeletal hyperostosis. Five percent of the patients showed progression of their abnormalities during the study. The difference in the rate of spur formation in the two groups may be due to multiple factors and not simply to retinoid therapy. Because of the extensive amount of preexisting disease in the psoriasis group compared with the relatively normal appearance of the spine in the isotretinoin group, the underlying disease process may be more important than the retinoid therapy. The development of the spinal spurs was not associated with specific clinical symptoms. Since there was no control group, it is unknown whether the spurs would have developed or progressed in the absence of retinoid therapy.

Topics: Acitretin; Adult; Humans; Isotretinoin; Psoriasis; Spinal Diseases; Time Factors; Tretinoin

Skeletal abnormalities have been reported on numerous occasions in patients who have received high doses of vitamin A and its derivatives. Recently, a new derivative, isotretinoin (Accutane, Hoffman-LaRoche, Inc.), has become available for the treatment of cystic acne. Ninety-six patients treated for a minimum of four months with low doses of this drug at two University centers have shown overall good to excellent clinical responses. However, ten of these patients have developed small pointed excrescences on the anterior margins of cervical, thoracic, or lumbar vertebral bodies. The findings are of unknown clinical significance but show some similarities to the spinal findings in DISH syndrome. Follow-up studies will be obtained, but, at the present time, the drug still can be recommended for patients who have severe cystic acne because of the excellent clinical response.

Topics: Acne Vulgaris; Adolescent; Adult; Exostoses; Female; Humans; Isotretinoin; Male; Radiography; Spinal Diseases; Tretinoin

Isotretinoin, a synthetic retinoid that has been prescribed for over 500,000 patients with cystic acne, has been associated with both spinal hyperostosis and a disorder similar to diffuse idiopathic skeletal hyperostosis. We describe a syndrome of tendon and ligament calcification, primarily in extraspinal locations, that we have observed after long-term therapy for psoriasis and disorders of keratinization with etretinate, another synthetic retinoid. Of 38 patients who had received etretinate (average dose, 0.8 mg per kilogram of body weight per day; average duration, 60 months), 32 (84 percent) had radiographic evidence of extraspinal tendon and ligament calcification. The most common sites of involvement were the ankles (29 patients [76 percent]), pelvis (20 patients [53 percent]), and knees (16 patients [42 percent]); spine involvement was uncommon in this group of etretinate-treated patients. Involvement tended to be bilateral and multifocal. Fifteen (47 percent) of the 32 affected patients had no bone or joint symptoms at the sites of radiographic abnormality. Thus, tendon and ligament calcification can occur without vertebral involvement as well as in association with it (for example, as part of the spectrum of diffuse idiopathic skeletal hyperostosis). We have identified extraspinal tendon and ligament calcification as a toxic effect that is commonly associated with long-term etretinate therapy.

Topics: Adult; Aged; Calcinosis; Etretinate; Female; Humans; Isotretinoin; Knee Joint; Ligaments; Lupus Erythematosus, Systemic; Male; Middle Aged; Pelvis; Prospective Studies; Psoriasis; Radiography; Skin Diseases; Spinal Diseases; Tendons; Tretinoin

Frequent symptoms of back and neck stiffness led to a radiographic investigation of the vertebral spine in patients receiving synthetic retinoids, isotretinoin and etretinate. X-ray examination of fifty patients with various skin disorders who received retinoids for at least 2 years were compared with seventy-two age- and sex-matched untreated patients. Differences in frequencies of defined abnormalities, which included anterior spinal ligament calcification and presence of osteophyte at two or more vertebral levels in the absence of joint space narrowing, were determined for treated and untreated patients. When the entire group of treated patients was compared with the entire group of those untreated, no statistically significant differences were observed. When only patients with basal cell nevus syndrome ( BCNS ) or basal cell carcinoma (BCC) who had never received retinoid were compared with those who received isotretinoin, the frequency of the defined abnormalities was significantly higher in the treated group (P less than 0.01). This study suggests that the ingestion of isotretinoin at mean total dose of 150,060 mg for an average of 2.9 years is associated with a statistically significant increase in developing an associated ossifying diathesis in patients with BCNS or BCC, when compared with matched, untreated controls.

Topics: Adult; Calcinosis; Dose-Response Relationship, Drug; Etretinate; Female; Humans; Isotretinoin; Male; Middle Aged; Radiography; Skin Diseases; Spinal Diseases; Spinal Osteophytosis; Spine; Tretinoin