Risedronate reduces the risk of first vertebral fracture in osteoporotic women.

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.

Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

OBJECTIVE: Risedronate, a new pyridinyl bisphosphonate, is a potent antiresorptive bone agent. This study examines the safety and efficacy of daily, oral risedronate therapy for the prevention of corticosteroid-induced bone loss. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted in 224 men and women who were initiating long-term corticosteroid treatment. Patients received either risedronate (2.5 mg or 5 mg) or placebo daily for 12 months. Each patient also received 500 mg of elemental calcium daily. The primary outcome measure was the percentage of change in lumbar spine bone mineral density (BMD). Secondary measures included proximal femur BMD and incidence of vertebral fractures. RESULTS: After 12 months, the lumbar spine BMD (mean +/- SEM) did not change significantly compared with baseline in the 5-mg (0.6 +/- 0.5%) or the 2.5-mg (-0.1 +/- 0.7%) risedronate groups, while it decreased in the placebo group (-2.8 +/- 0.5%; P < 0.05). The mean differences in BMD between the 5-mg risedronate and the placebo groups were 3.8 +/- 0.8% at the lumbar spine (P < 0.001), 4.1 +/- 1.0% at the femoral neck (P < 0.001), and 4.6 +/- 0.8% at the femoral trochanter (P < 0.001). A trend toward a decrease in the incidence of vertebral fracture was observed in the 5-mg risedronate group compared with the placebo group (5.7% versus 17.3%; P = 0.072). Risedronate was well tolerated, and the incidence of upper gastrointestinal adverse events was comparable among the 3 groups. CONCLUSION: Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment.

Tenidap in patients with rheumatoid arthritis. A 4-week, placebo-controlled study.

The present double-blind, placebo-controlled study was conducted to compare the safety and efficacy of tenidap in patients with rheumatoid arthritis (RA). Patients with flare of active RA following NSAID withdrawal were randomized to receive either placebo (n = 67) or tenidap (n = 131; 40-200 mg/day). The mean changes from baseline in efficacy and biochemical variables were compared between treatment groups at endpoint (4 weeks). The improvements in four of the five primary efficacy variables were significantly greater in the tenidap group compared with the placebo group (p < 0.01). Tenidap was also associated with an 18% reduction in erythrocyte sedimentation rate (ESR) and a marked, 51%, reduction in serum C-reactive protein (CRP) level, both of which were significantly greater than the changes in the placebo group (p < 0.05). The percentage of patients who discontinued because of side effects was the same in both groups (3%). In conclusion, tenidap 40-200 mg/day was effective and well tolerated in the treatment of patients with RA for 4 weeks.

The treatment of osteoarthritis of the knee with pulsed electrical stimulation.

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.

Strength training increases regional bone mineral density and bone remodeling in middle-aged and older men.

To determine the effects of strength training (ST) on bone mineral density (BMD) and bone remodeling, 18 previously inactive untrained males [mean age 59 +/- 2 (SE) yr] were studied before and after 16 wk of either ST (n = 11) or no exercise (inactive controls; n = 7). Total, spinal (L2-L4), and femoral neck BMD were measured in nine training and seven control subjects before and after the experimental period. Serum concentrations of osteocalcin, skeletal alkaline phosphatase isoenzyme, and tartrate-resistant acid phosphatase were measured before, during, and after the experimental program in all subjects. Training increased muscular strength by an average of 45 +/- 3% (P < 0.001) on a three-repetition maximum test and by 32 +/- 4% (P < 0.001) on an isokinetic test of the knee extensors performed at 60 degrees/s. BMD increased in the femoral neck by 3.8 +/- 1.0% (0.900 +/- 0.05 vs. 0.933 +/- 0.05 g/cm2, P < 0.05) and in the lumbar spine by 2.0 +/- 0.9% (1.180 +/- 0.06 vs. 1.203 +/- 0.06 g/cm2, P < 0.05). However, changes in lumbar spine BMD were not significantly different from those in the control group. There was no significant change in total body BMD. Osteocalcin increased by 19 +/- 6% after 12 wk of training (P < 0.05) and remained significantly elevated after 16 wk of training (P < 0.05). There was a 26 +/- 11% increase in skeletal alkaline phosphatase isoenzyme levels (P < 0.05) after 16 wk of training.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular lesions in SLE.

The confusing array of manifestations resulting from multisystem involvement in SLE is due, in part, to the widespread involvement of blood vessels.

Osteonecrosis.

Osteochondritis dissecans has been shown to heal with protective weight bearing alone, if there is no loose body in the joint. Magnetic resonance imaging can accurately predict the presence and extent of chondral fragments, and it appears that a magnetic resonance staging classification has been developed that allows preoperative staging of lesions of the talus and the knee. In a large study of hip dislocations, the most important predeterminant of poor clinical outcome was the presence of avascular necrosis. In addition to stigmata of rheumatoid arthritis, recognizable in 90% of 107 femoral heads in rheumatoid arthritis patients, 29 heads (28%) had intracapital trabecular fractures that were either the sole feature or a very important feature of the histopathology. In systemic lupus erythematosus patients the mean maximal daily dose of prednisone was significantly greater in patients with osteonecrosis than in those without bony complications. A novel canine model allowing investigations into the pharmacologic regulation of circulation in bone is discussed along with the first demonstration in humans of a pharmacologically produced decrease in bone marrow pressure. In spontaneous osteonecrosis of the knee, patients with magnetic resonance abnormalities on T2-weighted images have a poor clinical outcome. Magnetic resonance imaging of the hip can provide images of equal resolution in any plane, which is helpful in evaluating the extent and location of femoral head involvement. A large study revealed that total joint replacement should be done judiciously in osteonecrosis, because there is a 37% overall failure rate as compared to 10% failure rate in total hip replacements done for other causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous pulsed steroids in rheumatoid arthritis: a comparative dose study.

This prospective, double blind study was undertaken to test the efficacy of intravenous "minipulse" (100 mg) methylprednisolone (MP) therapy versus standard pulse (1000 mg) MP therapy in rheumatoid arthritis (RA). Thirty-six patients with RA synovitis flares were randomized to receive either 100 or 1000 mg MP IV QD x 3 doses. These 2 universally comparable groups exhibited no statistically significant differences in their striking prompt and sustained clinical improvement. These data suggest that minipulse MP is as efficacious as conventional pulse MP in the treatment of RA flares.

The predictive value of hemodynamic studies in preclinical ischemic necrosis of bone.

This study evaluated the predictive value of bone marrow pressures and intraosseous venography in joints at risk for developing ischemic necrosis of bone. Forty-two patients with ischemic necrosis of bone had hemodynamic studies performed on their contralateral, asymptomatic joint. A followup evaluation of symptoms and radiographs was obtained to establish the prevalence of clinical ischemic necrosis in the index joints. Thirty-six of 48 joints had increased bone marrow pressure and of these, 15 (42%) developed histologically or radiographically confirmed ischemic necrosis of bone. In none of the 12 bones with normal bone marrow pressure did ischemic necrosis of bone occur (p = 0.005). Venography was also significantly predictive for ischemic necrosis of bone, both alone and in conjunction with bone marrow pressure. Our study reaffirms the risk of developing bilateral ischemic necrosis of bone (31% at a mean followup of 47 months) once the diagnosis has been made on one side. Bone pressure measurements are of predictive value in establishing those joints which require close clinical followup so that detection of disease may be in the precollapse stage of ischemic necrosis of bone.

A long-term evaluation of the treatment of osteoarthritis.

In a study of the long-term safety and efficacy of piroxicam (20 mg daily) in the treatment of osteoarthritis, 30 female patients with a mean duration of more than seven years of treatment were evaluated. Despite having had poor or no response with other drug therapies, in the majority of cases in which piroxicam was used half of the patients (15 of 30) reported feeling very good or good at their last visit, 13 said they felt fair, and only two reported feeling poor or very poor in terms of their sense of well-being. The incidence of adverse events was somewhat less than one event per patient year of exposure, and 94 percent of adverse events were mild or moderate. Laboratory measurements of drug safety did not reveal any evidence of renal, hepatic, or hematologic toxicity. It is significant that patients were willing to commit themselves to long-term piroxicam therapy for at least five years after an initial trial and that they preferred to continue taking the drug rather than switch to alternative forms of therapy.

The early diagnosis of ischemic necrosis of bone.

One hundred sixty-nine patients with radiographic or histologic evidence of ischemic necrosis of bone (INB) were evaluated. Ninety-nine (59%) of the 169 patients had multiple sites of INB, with 310 bones affected. Two hundred sixty-three (85%) of the 310 ischemic bones were symptomatic. Routine radiography produced negative findings in 58 (20%) of the bones with histologically confirmed INB. Results of hemodynamic studies, including baseline bone marrow pressure, saline stress test, and/or intraosseous venography, were abnormal in 243 (94%) of 259 ischemic bones so evaluated. Most importantly, hemodynamic studies detected 51 (93%) of the 55 bones that were radiographically normal but had histologically confirmed INB.

Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus.

In this prospective study, 28 (52 percent) of 54 patients with systemic lupus erythematosus (SLE) had ischemic necrosis of bone in 93 sites. All but two of the patients had multiple sites of involvement, with hips, knees, and shoulders affected in decreasing order of frequency. Demographic, clinical, and laboratory features were comparable in patients with and without ischemic necrosis of bone except for cushingoid changes in 24 (86 percent) of the 28 patients with ischemic necrosis of bone versus four (15 percent) of the 26 patients without ischemic necrosis of bone (p less than 0.0001). The duration of steroid therapy, total cumulative steroid dose, and the mean daily prednisone dose for the first one, three, six, and 12 months of therapy were not significantly different between the two groups. Mean daily prednisone dose for the highest single month as well as the highest consecutive three, six, and 12 months of therapy was significantly higher in patients with ischemic necrosis of bone. The mean daily dose of prednisone for the highest month of therapy was greater than 40 mg per day in 93 percent and greater than 20 mg per day in all patients with ischemic necrosis of bone. In patients with ischemic necrosis of bone, there was a statistically significant correlation between higher mean prednisone dose at all time intervals and increased number of bony sites involved. A lower mean dose of prednisone was required to produce ischemic necrosis of bone in patients with Raynaud's phenomenon.

Long-term experience with piroxicam in osteoarthritis.

The long-term efficacy and safety of piroxicam 20 mg once daily in the treatment of osteoarthritis was evaluated in 30 patients--eight for three to five years, seven for six years, and 15 for more than seven years--for a total mean duration of six years. More than 93 percent (28/30) reported feeling well at the last visit, while 12 said they were either asymptomatic or had only mild symptoms. Total joint pain scores, total joint swelling and specific functional activity levels improved and remained improved throughout the study period. Side effects were relatively frequent but mostly in the mild to moderate class (159/166) and these were mostly gastrointestinal. Patients preferred remaining on the drug for a mean of six years rather than changing to alternative therapies made available to them.

Adult-onset Still's disease with an associated severe restrictive pulmonary defect: a case report.

A 21-year-old black female with an 18-month history of adult Still's disease developed symptoms and objective findings of restrictive lung disease. The pulmonary function abnormalities persisted unchanged for an additional 18 months despite moderate doses of prednisone. This complication has not been previously described in association with adult Still's disease.

Piroxicam in osteoarthritis: a controlled long-term study.

This six-month double-blind, parallel-design study compared the efficacy and safety of piroxicam 20 mg and 40 mg with that of 12 tablets of aspirin in 29 patients with osteoarthritis and demonstrated that both piroxicam doses were superior to aspirin in the treatment of osteoarthritis with respect to physicians' opinion of improvement and ease of movement. The safety of piroxicam 20 mg and aspirin were comparable, with gastrointestinal side effects being the most prevalent adverse effect. Patients receiving piroxicam are continuing in a five-year efficacy and safety study.

Comparison of bone scan and radiograph sensitivity in the detection of steroid-induced ischemic necrosis of bone.

A prospective study of bone scanning for detection of ischemic necrosis of bone (INB) was performed in 36 patients (97% female, age range 16-36 yrs.) with systemic lupus erythematosis (SLE). Since the hips, knees, and shoulders are usually affected by INB in patients with SLE, 300 K converging collimator images of these joints were obtained on film and in digital format 2 to 3 hours after the injection of 20 mCi (740 MBq) of Tc-99m methylene diphosphonate. All patients underwent radiography of the joints, and 10 had intraosseous pressure determinations in the marrow space of affected joints (n = 31) for independent assessment of INB. Scans showed abnormally increased joint activity in 28 of the 36 patients. A total of 97 joints showed abnormalities, 19% in the hips, 34% in the knees, and 47% in the shoulders. Twenty-four of 27 joints with elevated bone marrow pressure (BMP) had abnormal scans (sensitivity = 89%), and scans were abnormal in 2 of 4 joints with normal pressures (specificity = 50%). The positive predictive value of the scans compared with BMP measurements was 92% (24/26). Eleven of 27 joints with abnormal BMP had abnormal radiographs, a sensitivity of 41%.