Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis.

BACKGROUND: Degenerative lumbar spinal stenosis (LSS) is usually caused by disc herniation or degeneration. Several genetic factors have been implicated in disc disease. Tryptophan alleles in COL9A2 and COL9A3 have been shown to be associated with lumbar disc disease in the Finnish population, and polymorphisms in the vitamin D receptor gene (VDR) (FokI and TaqI), the matrix metalloproteinase-3 gene (MMP-3) and an aggrecan gene (AGC1) VNTR have been reported to be associated with disc degeneration. In addition, an IVS6-4 a>t polymorphism in COL11A2 has been found in connection with stenosis caused by ossification of the posterior longitudinal ligament in the Japanese population. OBJECTIVE: To study the role of genetic factors in LSS. METHODS: 29 Finnish probands were analysed for mutations in the genes coding for intervertebral disc matrix proteins, COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, and AGC1. VDR and MMP-3 polymorphisms were also analysed. Sequence variations were tested in 56 Finnish controls. RESULTS: Several disease associated alleles were identified. A splice site mutation in COL9A2 leading to a premature translation termination codon and the generation of a truncated protein was identified in one proband, another had the Trp2 allele, and four others the Trp3 allele. The frequency of the COL11A2 IVS6(-4) t allele was 93.1% in the probands and 72.3% in controls (p = 0.0016). The differences in genotype frequencies for this site were less significant (p = 0.0043). CONCLUSIONS: Genetic factors have an important role in the pathogenesis of LSS.

Cost effectiveness of periradicular infiltration for sciatica: subgroup analysis of a randomized controlled trial.

STUDY DESIGN: A subgroup analysis of a prospective, randomized controlled trial was performed. OBJECTIVE: To describe the cost effectiveness of periradicular infiltration with steroid in subgroups of patients with sciatica. SUMMARY OF BACKGROUND DATA: A recent trial on periradicular infiltration indicated that a methylprednisolone-bupivacaine combination had a short-term effect, as compared with that of saline. This report describes the efficacy and cost effectiveness of steroid in subgroups of patients with sciatic. METHODS: This study involved 160 patients with unilateral sciatica. Outcome assessments were leg pain (100-mm visual analog scale), disability on the Oswestry Low Back Disability Questionnaire, and the Nottingham Health Profile. Data on medical costs and sick leaves also were gathered. Patients were randomized for periradicular infiltration with either methylprednisolone-bupivacaine or saline. The adjusted between-group treatment differences at each follow-up assessment, the number of patients free of leg pain (responders, cutoff 75%), and efficacy by the area-under-the-curve method were calculated. For the cost-effectiveness estimate, the total costs were divided by the number of responders. The rate of operations in different subgroups was evaluated by Kaplan-Meier analysis. RESULTS: In the case of contained herniations, the steroid injection produced significant treatment effects and short-term efficacy in leg pain and in Nottingham Health Profile emotional reactions. For symptomatic lesions at L3-L4-L5, steroid was superior to saline for leg pain, disability, and straight leg raising in the short term. By 1 year, steroid seemed to have prevented operations for contained herniations, costing $12,666 less per responder in the steroid group (P < 0.01). For extrusions, steroid seemed to increase the operation rate, and the steroid infiltration was more expensive, costing $4445 per responder (P < 0.01). CONCLUSIONS: In addition to short-term effectiveness for contained herniations and lesions at L3-L4-L5, steroid treatment also prevented surgery for contained herniations. However, steroid was countereffective for extrusions. The results of the subgroup analyses call for a verification study.

Periradicular infiltration for sciatica: a randomized controlled trial.

STUDY DESIGN: A randomized, double-blind trial was conducted. OBJECTIVES: To test the efficacy of periradicular corticosteroid injection for sciatica. SUMMARY OF BACKGROUND DATA: The efficacy of epidural corticosteroids for sciatica is controversial. Periradicular infiltration is a targeted technique, but there are no randomized controlled trials of its efficacy. METHODS: In this study 160 consecutive, eligible patients with sciatica who had unilateral symptoms of 1 to 6 months duration, and who never underwent surgery were randomized for double-blind injection with methylprednisolone bupivacaine combination or saline. Objective and self-reported outcome parameters and costs were recorded at baseline, at 2 and 4 weeks, at 3 and 6 months, and at 1 year. RESULTS: Recovery was better in the steroid group at 2 weeks for leg pain (P = 0.02), straight leg raising (P = 0.03), lumbar flexion (P = 0.05), and patient satisfaction (P = 0.03). Back pain was significantly lower in the saline group at 3 and 6 months (P = 0.03 and 0.002, respectively), and leg pain at 6 months (13.5, P = 0.02). Sick leaves and medical costs were similar for both treatments, except for cost of therapy visits and drugs at 4 weeks, which were in favor of the steroid injection (P = 0.05 and 0.005, respectively). By 1 year, 18 patients in the steroid group and 15 in the saline group underwent surgery. CONCLUSIONS: Improvement during the follow-up period was found in both the methylprednisolone and saline groups. The combination of methylprednisolone and bupivacaine seems to have a short-term effect, but at 3 and 6 months, the steroid group seems to experience a "rebound" phenomenon.

Influence of estrogen-progestin treatment on back pain and disability among slim premenopausal women with low lumbar spine bone mineral density. A 2-year placebo-controlled randomized trial.

STUDY DESIGN: A 2-year randomized controlled trial. OBJECTIVES: To examine the possible preventive or aggravating effect of estrogen-progestin treatment on the back symptoms of slim premenopausal women with low lumbar spine bone mineral density. SUMMARY OF BACKGROUND DATA: The incidence of back pain, sciatica, or both starts to increase clearly among 45-54-year-old Finnish women. METHODS: Forty-eight 39- to 49-year-old premenopausal women with a body mass index of 21 or less and a lumbar spine bone mineral density (L2-L4) of 1.1 +/- 1 g/cm3 or less compared with the normative population were recruited into the study. The women were assigned randomly to receive either estradiol-noretisteron acetate treatment or placebo. Back pain, symptoms, and disability were assessed with the Million and Oswestry questionnaires and pain drawings during the follow-up period at 0, 12, and 24 months. Inquiry also was made concerning previous back pain and sciatica history. RESULTS: There was a statistically significant decrease in nighttime back pain (P < 0.001) and the total Oswestry disability scores (P < 0.004) in the hormone-treated group compared with the control group during the follow-up, but no statistically significant differences were found in daytime back pain. At baseline, the cumulative incidence in a history of pain radiating from the buttock to the foot in this osteopenic study group was 31/48, (64.5%; 95% CI 50.5-78.6), which is much more than the predicted 20/48, (42.4%; 95% CI 39.0-45.7) at this age according to a previous population study. The cumulative incidence of at least one back pain episode 44/48, (91.7%; 95% CI 83.6-99.8) was somewhat higher in these participants than was predicted for a comparative population of women this age, 38/48 (79.2%; 95% CI 70.2-87.3). CONCLUSIONS: It seems that this regimen may have alleviating effects on nighttime back pain and functional back disability in slim osteopenic premenopausal women.

Influence of estrogen-progestin replacement therapy and exercise on lumbar spine mobility and low back symptoms in a healthy early postmenopausal female population: a 2-year randomized controlled trial.

The purpose of this study was to examine the influence of estrogen-progestin replacement therapy and exercise on the lumbar spine mobility and back symptoms of early postmenopausal women. The population sample consisted of 78 healthy, 49- to 55-year-old women, 0.5-5 years after menopause, who were randomized into three groups, two receiving different protocols of estradiol valerate combined with medroxyprogesterone acetate replacement therapy, and the third group a placebo. These groups were then randomized into exercise and control cases and monitored for 2 years. The mobility of the lumbar spine was measured and symptoms investigated using the Million and Oswestry pain and disability questionnaires and pain drawings at the baseline and after 1 and 2 years. During the follow-up, the mobility of the lumbar spine decreased in all six groups. The decrease was most evident in those who had been the most flexible at baseline (P < 0.0001). The decrease was less notable in the hormone replacement therapy groups than in the control group. When the replacement therapy groups were pooled together, the difference was significant at a P < 0.05 level. No difference was seen between the hormone combinations. The exercise intervention was insufficient to influence lumbar spine mobility. Only sporadic cases of back symptoms appeared and disappeared among the subjects during the follow-up, and no preventive or aggravating effects of hormone replacement therapy or the exercise program on symptoms were detected.

HRT and exercise: effects on bone density, muscle strength and lipid metabolism. A placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women.

OBJECTIVES: To evaluate the effect of 1- or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women. METHODS: Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E2V tablets for 11 days, followed by 2 mg E2V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E2V for 70 days, 2 mg E2V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups. RESULTS: Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens. CONCLUSIONS: Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol.

A study of the effects of lisinopril when used in addition to atenolol.

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.

Comparison of muscle strength and bone mineral density in healthy postmenopausal women. A cross-sectional population study.

In this cross-sectional population study with 78 healthy 0.5-5 years postmenopausal, 49-55 year old females a significant simple linear correlation between lumbar spine LII-LIV bone mineral density and adjacent back extensor and flexor isometric muscle strength was found. With the stepwise multiple linear regression analyses the most significant predictors for lumbar spine LII-LIV and femoral neck bone mineral density were weight (partial R2) (R2 = 0.197, p = 0.0001; R2 = 0.157, p = 0.0009) and age (R2 = 0.056, p = 0.0205; R2 = 0.036, p = 0.0708). Height and isometric muscle strength and endurance of muscles were not significant predictors. Weight and age were the most significant predictors also for isometric muscle strength. The mobility of spine, body fat content and anaerobic threshold had no correlation on bone mineral density.

Moderate exercise does not enhance the positive effect of estrogen on bone mineral density in postmenopausal women.

We studied the effects of physical activity and two types of estrogen treatment in a prospective study in 78 healthy postmenopausal women. A control group and two treatment groups receiving estradiol valerate and medroxyprogesterone acetate in 1- or 3-month cycles were monitored for 1 year. Half of each group took part in an exercise program. Lumbar and femoral bone mineral density increased in both of the estrogen-treatment groups. Physical exercise with estrogen treatment did not result in further increases in bone mineral densities.