RESUMEN
Three female patients, aged 76, 64 and 74 years old, who were treated with low-dose methotrexate due to an inflammatory joint disorder, developed severe pain in a lower extremity. The pain increased on weight bearing and could not be explained by arthritis. Conventional x-ray investigation showed a fracture in the second patient. In the other two patients insufficiency fractures were visualized by MRI and bone scan. Because methotrexate osteopathy was suspected, treatment with methotrexate was stopped. All three patients made a rapid recovery after discontinuation. Methotrexate osteopathy is characterized by pain, osteoporosis and microfractures, and was first reported in children treated with high-dose methotrexate for a malignancy. Similar clinical features are reported in the literature in patients with chronic joint inflammation treated with low-dose methotrexate. The causal relationship between the insufficiency fractures and the use of methotrexate is still under debate. Although the clinical picture fits with methotrexate osteopathy, these patients often also have other risk factors for osteoporotic insufficiency fractures.
Asunto(s)
Enfermedades Óseas Metabólicas/inducido químicamente , Fracturas por Estrés/inducido químicamente , Inmunosupresores/efectos adversos , Metotrexato/efectos adversos , Osteoporosis/inducido químicamente , Anciano , Enfermedades Óseas Metabólicas/patología , Femenino , Fracturas por Estrés/patología , Humanos , Inmunosupresores/uso terapéutico , Inflamación/tratamiento farmacológico , Imagen por Resonancia Magnética , Metotrexato/uso terapéutico , Persona de Mediana Edad , Osteoporosis/patología , Remisión EspontáneaRESUMEN
The administration of moderate to high doses of corticosteroids is associated with bone loss. This probably results from the uncoupling of bone formation (decreased) and bone resorption (unchanged or increased). We examined the effect of low-dose (10 mg/day) prednisone (LDP) and the possible mitigating effects of calcium and 1.25 (OH)2 vitamin D (calcitriol) on calcium and bone metabolism in eight healthy, young male volunteers. The study consisted of four observation periods: in the first period, LDP was prescribed during 1 week; in the second, third and fourth periods, calcium (500 mg/day), calcitriol (0.5 micrograms b.i.d.) and calcium in combination with calcitriol, respectively, were added to LDP. Bone formation was measured by means of serum osteocalcin, carboxy-terminal propeptide of type 1 procollagen (P1CP) and alkaline phosphatase, bone resorption by means of urinary excretion of calcium, hydroxyproline, (free and total) pyridinoline, (free and total) deoxypyridinoline and serum carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP). Dietary calcium and sodium intake were maintained at a stable level during the entire study period. Treatment with LDP led to a decrease in osteocalcin, P1CP and alkaline phosphatase (all P < 0.01). Urinary excretion of pyridinolines, hydroxyproline and serum 1CTP did not increase, but remained unchanged or slightly reduced (P < 0.05), depending on the time of measurement and the marker of bone resorption. Parathyroid hormone (PTH) (insignificantly) increased during LDP (+19%) and LDP plus calcium (+14%), but decreased during supplementation with calcitriol (-16%) and calcium/calcitriol (-44%; P < 0.01). Urinary excretion of calcium increased during treatment with LDP and calcitriol (P < 0.05) and calcium/calcitriol (P < 0.05). It is concluded that LDP has a negative effect on bone metabolism, since bone formation decreased while bone resorption remained unchanged or decreased slightly. The increase in PTH during LDP could be prevented by calcitriol combined with calcium supplementation.
Asunto(s)
Huesos/metabolismo , Calcio/metabolismo , Prednisona/administración & dosificación , Adulto , Fosfatasa Alcalina/sangre , Huesos/efectos de los fármacos , Calcitriol/administración & dosificación , Calcio/administración & dosificación , Glucocorticoides/administración & dosificación , Humanos , Masculino , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , Procolágeno/sangreRESUMEN
OBJECTIVE: To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids. PATIENTS AND METHODS: 47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months. RESULTS: After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p < 0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: -2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p < 0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: -2.5% (95% CI: -6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: -4.0% (95% CI: -6.6% to -1.4%; p < 0.01). The difference between the groups was not significant: +1.5% (95% CI: -3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups. CONCLUSION: The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.