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Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy. [ABSTRACT FROM AUTHOR]

The hand is commonly affected by osteoarthritis (OA). The development and progression of OA are believed to involve inflammation, even in the early stages of the disease. Inflammatory and proinflammatory cytokines have also been shown to be elevated in the flexor tenosynovium of idiopathic carpal tunnel syndrome (CTS). A large percentage of patients with hand OA also have a concomitant CTS. This study evaluated the results of a pulsed electrical joint stimulator in patients who had hand OA with or without CTS. Pain, tenderness, and swelling; grip strength and pinch force; and Patient and Physician Global Assessment and Disabilities of the Arm, Shoulder and Hand (DASH) results were evaluated. The primary efficacy outcome was pain due to OA in the study hand in the past 48 hours. Secondary outcomes consisted of OA pain in the study thumb in the past 48 hours, grip strength, pinch force, and Patient and Physician Global Assessment and DASH results. All 7 outcome parameters improved in OA patients. On physical examination, individual finger and wrist joints had also improved regarding pain, swelling, and tenderness. In the subset of patients with CTS, CTS pain, paresthesia, weakness, and all CTS symptoms had significantly improved. Patient and Physician Global Assessment and DASH results and pinch force were also significantly improved. This pulsed electrical joint stimulator is effective in providing clinically relevant and statistically significant reductions in the signs and symptoms of OA of the hand and CTS. It could be a useful modality for the treatment of patients who have one of these conditions or both. [Orthopedics. 2018; 41(4):e550-e556.]., (Copyright 2018, SLACK Incorporated.)

Medical treatments and less invasive surgical approaches for knee osteoarthritis are variably effective, and total knee arthroplasty (TKA) is generally reserved for the most severe cases. The care gap between more conservative treatments and TKA leaves many patients with unresolved pain and loss of function for long periods. We conducted a study to determine if incorporating the BioniCare stimulator into an unloading brace would produce more rapid improvement and result in increased adherence and efficacy. Two hundred eighty-nine patients treated only with BioniCare served as historical controls and were compared with 225 patients treated with BioniCare combined with an unloading brace. Means and standard deviations of the changes in scores for pain intensity in the past 48 hours, pain and associated symptoms, patient global assessment, pain on going up or down stairs, and pain on walking on a flat surface and the effect sizes at 1, 3, 6, and 12 months, as well as the percentages of patients achieving at least 20% improvement, and at least 50% improvement, demonstrated that treatment with stimulator and unloading brace combined was significantly superior to treatment with the stimulator alone.

Background: Optimized pulsed electrical stimulation (PES) regulates chondrocyte genes, enhances production of cartilage matrix materials, and inhibits production of matrix catabolic factors., Methods: This prospective, cohort study examined the use of a PES device in treatment of knee osteoarthritis (OA) in patients who had failed non-operative therapy. Primary outcome measures were patient and physician global evaluation, and patient assessment of knee pain., Results: This study included 288 (95 men, 193 women) patients who used the device from 16 to more than 600 days (mean: 889 hours). Improvement in all efficacy variables (p < 0.001) occurred. A dose-response relationship between effect size and hours of usage was observed as cumulative time increased to more than 750 hours. Improvement in patient or physician global occurred in 59.0% of patients who used it less than 750 hours, and for 73.0% of those who used it more than 750 hours. An economic analysis of a sub-group of patients showed that 45.3% reduced nonsteroidal anti-inflammatory drug (NSAID) use by 50.0% or more., Conclusions: A highly optimized PES device successfully attenuated knee OA symptoms in patients who had failed non-surgical therapy. Less than 250 hours of therapy provided relief, but improvement increased in a dose-response manner after 750 hours of cumulative use.

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.

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.

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.

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.

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)

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

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)

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.

Fifteen (11 percent) of 140 patients with systemic lupus erythematosus (SLE) and five (31 percent) of 16 patients with polyarteritis nodosa (PA) developed disease-related signs and symptoms of an acute surgical abdomen. Peripheral vasculitis (p less than 0.025), nervous system involvement (p less than 0.05), ischemic necrosis of bone (p less than 0.05), thrombocytopenia (p less than 0.01), and circulating rheumatoid factor (p less than 0.01) are all significantly more prevalent in patients with SLE and abdominal involvement compared with those without an abdominal syndrome. Similarly, except for ischemic necrosis of bone, these same features are more prevalent in patients with PA and acute abdomens. Eleven (73 percent) of 15 patients with SLE had exploratory laparotomy for acute abdominal events. Nine were found to have evidence of intra-abdominal arteritis and only two had polyserositis without gross evidence of vasculitis. Eight (53 percent) of the 15 patients with SLE and acute abdomens died as a result of their abdominal crises. Six of the seven surviving patients represent those most recently seen and aggressively treated. All five patients with PA and acute abdomens required operative intervention and all had gross evidence of mesenteric arteritis with large ischemic segments resulting in infarction and perforation. All died in contrast to only two (18 percent) of the 11 PA patients without abdominal involvement.

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%.

Sixty-two patients with popliteal or calf synovial cysts defined by arthrography are presented, of whom 34 had the pseudothrombophlebitis (PTP) syndrome. While the clinical manifestations of PTP may closely mimic thrombophlebitis, including the presence of calf pain, swelling and warmth, and a positive Homans' sign, the helpful descriminating features include the presence of inflammatory joint disease (91%), concomitant pain and swelling of the knee (94%), a demonstrable knee effusion (91%) and the absence of deep venous tenderness or cord. Except for seven patients with large intact Baker's cysts, the PTP syndrome was associated with synovial cyst dissection (18 patients), rupture (5 patients), or both (4 patients). Of those with arthrographically demonstrated Baker's cysts, only 27 (44%) had a palpable mass in the popliteal fossa and another 4 (12%) a mass in the calf. Popliteal fossa pain was noted in 22 (35%). Thus, clinical features are far less sensitive than arthrography in the diagnoses of both synovial cysts and pseudothrombophlebitis. Among patients with rheumatoid arthritis there were no differences in the severity or duration of disease or the extra-articular features in patients with and without synovial custs or the PTP syndrome. The therapeutic implications of pseudothrombophlebitis are of major significance with respect to the avoidance of anti-coagulation and the prompt response to intra-articular corticosteroids. Possible mechanisms of synovial cyst formation and unusual presentations of synovial cysts are discussed, and the literature is reviewed.

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.

We present an in-depth study of rheumatoid arthritis (RA) in a Chippewa band. Of the 227 band members, 168 (74%) were evaluated. The unusually high prevalence of RA was confirmed in 7.1% of those studied or, minimally, 5.3% with a 100% completion rate without additional cases found. Seropositivity in those with clinically definite RA was 92% relative to rheumatoid factor and 75% for ANA. Despite the high prevalence (68%) of HLA-DR4 in this closed population, there was a significant correlation of DR4 with RA (100%). The implications of these observations in this population isolate are discussed.

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.

Five patients with systemic lupus erythematosus (SLE), four of whom died with colonic perforations, are reported. Perforation of the colon constituted the most frequent cause of death among 107 patients with SLE admitted to the Rheumatic Disease Unit during a three year period. All five patients with colonic perforation had clinical and laboratory manifestations of active SLE in addition to the abdominal syndrome. Most striking was evidence of active arteritis in all patients with either central nervous system involvement and/or peripheral arteritis, in addition to that found in the gastrointestinal tract. Hyperglobulinemia and rheumatoid factor as well as antinuclear antibodies were present at some time in all patients. The abdominal syndrome was characterized by the insidious onset of lower quadrant pain which was intermittent and colicky. Although direct abdominal tenderness was eventually present in all patients, rebound tenderness and hypoactive bowel sounds were variable and abdominal rigidity occurred only in one patient and late in the course. The differential diagnosis of abdominal pain in SLE is reviewed and possible mechanisms for the production of colonic perforations are discussed. It is suggested that the presence of rheumatoid factors in conjunction with circulating immune complexes may be the pathogenetic mechanism via the production of a mesenteric arteritis.

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.

Relapsing polychondritis is a disorder of unknown cause characterized by the destruction of cartilage. To test the hypothesis that immunologic mechanisms are involved in the pathogenesis of relapsing polychondritis, we analyzed the serum of 15 patients for the presence of antibodies to cartilage. Antibodies to Type II (cartilage) collagen were found in the serum of five patients at the time of acute symptoms. No antibodies were detected either to cartilage proteoglycan or to other collagen types. The antibodies were detected at the onset of the disease and their titers appeared to correlate with severity of disease. Circulating immune complexes were also detected in the serum of these patients. Our findings support an immunologic involvement in this condition.

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.

There are several potential pathways by which bone dies, one or more of which may be operative in any given case. However, the compartmental nature of its circulation renders bone vulnerable to ischemia from a primary elevation of BMP due to increase in any of the tissues within bone and outside the vessels. Furthermore, ischemia from other primary sources may be potentiated by a secondary increase in BMP. Findings of elevated BMP in the preradiologic and even preclinical stages of INFH support this pathogenetic hypothesis. The long-term results of core decompression reported by Professor Ficat lend further credence to these concepts.

Thirty-eight hips in 26 patients with alcoholism associated ischemic necrosis of the femoral head (INFH) have been evaluated by measurement of intraosseous pressure, (IOP) pressure response to a 5 ml saline load injected intraosseously and intraosseous venography. All stages of INFH were characterized by elevated IOP and/or an increased pressure response to the saline load compared to normal controls. Intraosseous venography in INFH was characterized by poor or absent visualization of the main efferent veins draining the proximal femur, diaphyseal reflux and delayed evacuation of dye from the bone. It has been possible to identify both a preradiologic and even preclinical stage of INFH. Core decompression, the removal of an 11 mm plug of bone from the head and neck of the femur, has been carried out on all hips in the study. All patients had pain prior to surgery. Eight patients in Stage I (preradiologic stage) are symptom free and without radiologic progression at follow-up, average 24 months. Only one of 5 patients in Stage II (no collapse of the femoral head) has shown X-ray progression while all remain asymptomatic. In Stage III (collapse, without acetabular involvement), core decompression offers relief of symptoms but does not appear to prevent further head collapse.

Seven (9.2%) of 76 patients with adult-onset polymyositis/dermatomyositis (PM/DM) seen over an 11-year period had cutaneous vasculitis. This was manifest by dermal and/or subcutaneous nodules in 4, periungual infarcts in 3 and digital ulceration in 2. When these 7 patients were compared to the remaining 69, a significant association was noted between cutaneous vasculitis and DM (p = .025); only 1 of 31 patients with primary PM and none of 18 with overlap syndromes had vasculitis. Furthermore, 2 (28.6%) of those with vasculitis had an associated malignancy compared to only 4 (5.8%) of those without vasculitis. These data document the occurrence of cutaneous vasculitis in adult-onset PM/DM and suggest that its presence may be a marker of an underlying malignancy.

Behçet's disease, originally described as a triad of ocular inflammation and oral and genital ulcerations, is better understood as a mulitsystem disease involving skin, joints, central nervous system, large bowel, and peripheral veins. This report of a 49-year-old female patient with uveitis and recurrent orogenital lesions, polyarthritis, and skin lesions, serves as introduction to a review of articular involvement in Behçet's disease. Included is complete synovial fluid analysis with measurement of intraarticular complement. Arthropathy, occurring in at least one-half of reported patients, is usually polyarticular and asymmetrical. It affects knees and ankles most frequently and rarely produces loss of function or deformity. During exacerbations synovial fluid appears inflammatory with polymorphonuclear leukocytosis greater than 25,000 cells/mul; synovial fluid complement is consistently elevated. Histologically the synovium shows increased vascularity with perivascular lymphocyte infiltration. Etiology and treatment of Behçet's disease are briefly discussed.

Antigen-antibody interaction and fibrin deposition at the glomerular basement membrane can release activators that ultimately convert fibrin into degradation products of varying molecular size. Thus, increased urinary fibrinogen/fibrin split products (FSP) might be expected in active lupus nephritis. A longitudinal study was done on 27 patients with biopsy-proven lupus nephritis. Those patients who were persistent FSP excretors were found to be at a significantly greater risk of progressive nephritis and renal death than those who were FSP negative. It is suggested that FSP excretion in lupus nephritis, particularly on a continued basis and despite normalization of other renal disease parameters, is a grave prognostic sign.

It would appear from our experience thus far, that increased bone marrow pressure and altered venous drainage, as documented by venography, are present in all stages of ischemic necrosis of bone, including the pre-radiologic, and may be the earliest detectable changes in this disorder. This implies that any postulated pathogenetic mechanism must take into account the early appearance of significant venous derangement, although not necessarily indicating that the venous abnormalities are primary. The data indicate that the venous circulation participates in and undoubtedly contributes to the progression of the disorder. In addition the successful results of core decompression reported in Part II, lend support to such a pathogenetic sequence, and may well be due to the interruption of this vicious circle.

Twenty-three patients with systemic lupus erythematosus (SLE) and ischemic bone necrosis are reported. All patients had received corticosteroids prior to the onset of ischemic necrosis, although one patient had received none for 13 years previously. Nineteen (83%) patients had multiple bone lesions including the femoral heads in 21 (91%) which were bilaterally involved in 15. In addition, humeral heads were affected in seven patients and the tibial plateaus, in three. The most striking feature of this group was the high incidence of Raynaud's phenomemon present in 14 (61%) of the 23 patients. Furthermore, central nervous system involvement was present in 10 (43%) patients, more prominent in those without Raynaud's (67%) than in those with vasospasm (29%). Thus, 20 of the 23 patients, or 87%, evidenced vascular abnormalities either in the form of Raynaud's phenomenon and/or systemic vasculitis. The pathogenesis of ischemic bone necrosis is discussed. In SLE, vasospasm or vasculitis, or both, augmented by corticosteroid therapy, could impede the microcirculation and result in the ischemic lesion.

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.

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.

1. Among patients with SLE, 71 (51%) had significant neuropsychiatric problems during the course of the disease. In 52 (37%), the nervous system manifestations were secondary to SLE. 2. The most frequent manifestations were psychiatric dysfunction, seizures, long tract signs, cranial neuropathy, and peripheral neuropathy. 3. Psychiatric abnormalities secondary to SLE were characterized by organic features (present in 22 of 24) and by the association of neurologic lesions which were often diffuse or multifocal. 4. An abnormal cerebrospinal fluid was found in 32% of neuropsychiatric episodes in which specimens were obtained. The most frequently abnormal study was the electroencephalogram (71%), and the least frequent was the brain scan (8%). These studies did not correlate with specific clinical patterns. 5. In 63% of the patients, NP manifestations preceded the diagnosis of SLE or occurred within the first year of diagnosed disease, and in most episodes were associated with evidence of clinical and/or serologic activity of the underlying illness. 6. Only two clinical features showed significant and striking correlations with neuropsychiatric involvement, namely vasculitis and thrombocytopenia. The possible pathogenic implications have been discussed. 7. Only 2 of the 140 patients were felt to have steroid-induced psychoses. In approximately one-half of the NP episodes secondary to SLE, patients were receiving no corticosteriods on presentation. Of those developing while patients were on steroids, the majority occurred on low doses or after tapering from higher levels. 8. The immediate prognosis for improvement in neuropsychiatric function was good with 84% of episodes showing complete or partial resolution. Corticosteroids appeared to be of benefit in a substantial number of patients although their precise role is difficult to quantitate. 9. Five and 10 years survivals for the overall population were 94% and 82%, respectively. There were no significant differences in survival for patients with or without nervous system involvement.

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.