[Establishment of a rat model of cervical syndrome with kidney deficiency].

OBJECTIVE: To establish a rat model of cervical syndrome (CS) with kidney deficiency. METHODS: A group of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal control group, CS group and CS with kidney deficiency group (combined group), with 10 rats in each group. Rats in the normal control group received no treatment, rats in the CS group underwent only resection of cervical muscles and ligaments as unbalanced dynamic and static animal model, and rats in combined group underwent resection of both cervical muscles and ovaries as kidney deficiency model. Serum and cervical intervertebral discs were collected. Kidney deficiency was determined by observing the morphologic changes of uterus and appendages, detecting the weight of uterus and appendages and the content of serum estradiol (E(2)). The degeneration of intervertebral discs was determined by detecting the histopathology, the expressions of type II collagen and type X collagen proteins, and the expressions of aggrecan-1 (Agc1), type II procollagen gene (Col2a1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs. RESULTS: Compared with those in the normal control group and CS group, the rats in the combined group were noted with the uterus atrophied, the caliber of oviduct thinned, the weight of uterus and appendages diminished obviously, the content of serum E(2) decreased, cervical intervertebral disc degenerated more seriously, type II collagen protein expression decreased, type X collagen protein expression increased, Agc1 and Col2a1 mRNA expressions in intervertebral disc decreased, and the MMP-13 mRNA expression increased. CONCLUSION: The rat model of CS with kidney deficiency is established. Kidney deficiency can aggravate cervical intervertebral disc degeneration.

[The design of a model of the experimental cervical spondylosis].

A model of the cervical spondylosis in the rabbits was established with press-injection of saline into the space between C5 and C6. The formation of the osteophytes at the posterior corner of the vertebra and the slight compression of the spinal cord were found in 4 months after the injection. The swelling, degeneration and rupture of the annulus fibrosus, the regeneration of fibrocartilage cells and the deposition of calcium extending to the posterior part of the vertebral body were observed under light microscope. The pathological changes were similar to those of the cervical spondylosis in the human being.

Extensive spinal hyperostosis in a patient receiving isotretinoin--progression after 4 years of etretinate therapy.

A patient with Darier's disease was discovered to have persistent, asymptomatic cervical and thoracic spinal hyperostoses after receiving isotretinoin for 7 years. The spinal abnormalities have remained asymptomatic but have now progressed following 4 years of etretinate therapy. The development of skeletal abnormalities, in particular spinal hyperostosis, is well-documented in patients receiving the synthetic retinoid, isotretinoin (Accutane, Roaccutane). The occurrence of extraspinal tendon and ligament calcification has been emphasized following long-term therapy with etretinate (Tegison, Tigason), but the relationship between etretinate and spinal hyperostosis is less certain, there being a need for a long-term, prospective, appropriately controlled investigation of patients receiving etretinate. We report a patient with Darier's disease who was discovered to have prominent, asymptomatic cervical and thoracic spinal hyperostoses after receiving isotretinoin for 7 years. Subsequent treatment with etretinate for 4 years did not prevent progression of the spinal abnormalities.

Skeletal hyperostosis and extraosseous calcification in patients receiving long-term etretinate (Tigason).

In an ongoing study of patients on long-term etretinate (Tigason) therapy, 13 patients with a congenital or inherited disorder of keratinization and 10 patients with psoriasis were examined to investigate the incidence of, and the factors associated with, skeletal hyperostosis. Skeletal scintigraphy, plain radiographs, haematological and biochemical analyses were performed. Using all criteria, 7 of 13 patients with a congenital or inherited disorder of keratinization showed evidence of hyperostosis. No single investigation was able to detect all these cases; in particular, skeletal scintigraphy was positive in only nine of the 13 patients who showed hyperostosis. Eleven of the 13 patients with hyperostosis gave a history of musculoskeletal symptoms compared with three of the 10 patients without hyperostosis. There was no clear association with total dose or duration of treatment. Serum chemistry and haematological studies were normal. In two patients the 24-h urinary calcium excretion was significantly elevated, an abnormality which has not been described previously. Annual lateral thoracic spine radiographs with additional views of symptomatic areas are recommended for patients on long-term etretinate therapy.

Skeletal toxicity with isotretinoin therapy: a clinico-radiological evaluation.

Skeletal toxicity is known to occur with high doses of isotretinoin (greater than 2 mg/kg/day). We have attempted to evaluate the clinical significance and document the extent of musculoskeletal toxicity associated with a relatively low dose of isotretinoin (0.5 mg/kg/day) used in the treatment of severe acne. Radiographs of 120 patients were examined. Twelve per cent showed minor changes (four patients had spinal hyperostoses and 10 had calcaneal hyperostoses). None of the musculoskeletal changes we observed was clinically significant. Comparison with matched control X-rays showed 8% of the controls to have similar non-significant changes. Follow-up of 11 of the patients with abnormal X-rays showed minor deterioration in one patient, no change in four and improvement in six. Thus, doses of 0.5 mg/kg/day isotretinoin in such patients did not produce any significant long-term musculoskeletal changes. With increasing use of this beneficial drug in acne, radiologists and dermatologists should be aware of its skeletal toxicity.

[Skeletal changes following long-term treatment with retinoids]. / Skelettveränderungen nach Langzeitbehandlung mit Retinoiden.

The synthetic retinoids, the vitamin-D-derivatives etretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication.

The spectrum of skeletal changes associated with long-term administration of 13-cis-retinoic acid.

The roentgenographic changes noted in 13 patients, who had been treated with long-term 13-cis-retinoic acid for inherited scaling disorders, are presented. These patients were aged 13-16 years and had received this therapy for 16-87 months (mean, 58 months). The most pronounced abnormality was osteophyte formation, particularly in the cervical spine. Other changes which were noted included ossification of the anterior longitudinal and atlanto-occipital ligaments, proliferative enthesopathies, diminished bone density, premature fusion of epiphyses, and modeling abnormalities. Six of the 13 patients were asymptomatic and the osseous manifestations of this therapy were identified only by roentgenographic evaluation.

Skeletal changes associated with chronic isotretinoin and etretinate administration.

The skeletal changes associated with systemic retinoid therapy reflect the influence of retinoids on differentiating systems. Although skin is usually the intended target, treatment with retinoids often results in abnormalities of ossification and calcification. The effects of retinoids on bone may be profound and include progressive calcification of ligaments and tendon insertions, premature fusion of epiphyses, modeling abnormalities of long bones, and perhaps osteoporosis. Although it has been known since 1933 that vitamin A cause bone abnormalities, the mechanism of this effect has been elusive. Recent work suggests a possible relationship of the retinoids with several cytokines, which results in enhanced maturation of the preosteoclast. The increasing number of significant bone changes, including posterior lumbar vertebral osteophytosis, make skeletal toxicity the principle risk factor of chronic systemic retinoid therapy.

Vertebral abnormalities associated with synthetic retinoid use.

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.