Search

Calcitonin reduces the risk of vertebral fracture in postmenopausal women with osteoporosis. Calcitonin produces small increments in the bone mass of the spine and modestly reduces bone turnover in women with osteoporosis. No significant effect on nonvertebral fractures has been observed. Calcitonin may have analgesic benefit.

Context: Vertebral fractures significantly increase lifetime risk of future fractures, but risk of further vertebral fractures in the period immediately following a vertebral fracture has not been evaluated., Objective: To determine the incidence of further vertebral fracture in the year following a vertebral fracture., Design and Setting: Analysis of data from 4 large 3-year osteoporosis treatment trials conducted at 373 study centers in North America, Europe, Australia, and New Zealand from November 1993 to April 1998., Subjects: Postmenopausal women who had been randomized to a placebo group and for whom vertebral fracture status was known at entry (n = 2725)., Main Outcome Measure: Occurrence of radiographically identified vertebral fracture during the year following an incident vertebral fracture., Results: Subjects were a mean age of 74 years and had a mean of 28 years since menopause. The cumulative incidence of new vertebral fractures in the first year was 6.6%. Presence of 1 or more vertebral fractures at baseline increased risk of sustaining a vertebral fracture by 5-fold during the initial year of the study compared with the incidence in subjects without prevalent vertebral fractures at baseline (relative risk [RR], 5.1; 95% confidence interval [CI], 3.1-8.4; P<.001). Among the 381 participants who developed an incident vertebral fracture, the incidence of a new vertebral fracture in the subsequent year was 19.2% (95% CI, 13.6%-24.8%). This risk was also increased in the presence of prevalent vertebral fractures (RR, 9.3; 95% CI, 1.2-71.6; P =.03)., Conclusion: Our data indicate that women who develop a vertebral fracture are at substantial risk for additional fracture within the next year.

Objective: To determine the reliability, consistency, and clinical utility of the Osteoporosis Assessment Questionnaire (OPAQ), an AIMS2 based self-assessment questionnaire., Methods: Reliability of individual questions, scales, and domains were evaluated in 40 subjects by test-retest and intraclass correlation coefficients and internal consistency by Cronbach's alpha. Construct validity was evaluated by disease state. The relationships between domains and scales were modeled by confirmatory factor analysis., Results: Mean kappa (79 questions) and intraclass correlation (18 health scales) coefficients were 0.58+/-0.16 (mean+/-SD) and 0.82+/-0.07, respectively. Internal consistency was greater than 0.8 in all but 3 scales. Construct validity was confirmed. Patients with hip fracture recorded lower OPAQ scores than patients with vertebral fracture. Correlation and confirmatory factor analyses grouped the 18 health scales into 7 domains., Conclusion: These findings suggest that OPAQ is a reliable, consistent, and valid instrument capable of distinguishing hierarchy of functional loss in disease states in osteoporosis.

Quality of life measurement may be helpful in randomized clinical trials in osteoporosis to assess therapeutic tradeoffs and compare effects of different interventions. Quality of life measures include generic measures, disease targeted measures, and performance based measures. Disease targeted measures increase the coverage of domains that are of particular importance to the patient with established osteoporosis. Several disease targeted measures are currently available. These measures show discriminant validity, but data on longitudinal responsiveness and validity in randomized clinical trials are not yet available.

Nasal calcitonin is a newly approved treatment for established osteoporosis that increases lumbar spine bone mass, is safe, and well tolerated. Fracture efficacy data is not yet available, although preliminary results are promising. The dose for established osteoporosis is 200 IU. The dose for prevention of postmenopausal osteoporosis has not been established. Nasal calcitonin may be analgesic to bone and may be of benefit in glucocorticoid-induced vertebral osteoporosis. Nasal spray calcitonin may be of benefit to the symptomatic patient with acute vertebral fracture, the complex patient, or the patient with established osteoporosis who is intolerant of bisphosphonates or estrogen.

Nasal calcitonin is a newly approved treatment for established osteoporosis. Nasal calcitonin is safe, preventative, and may increase bone mass in the lumbar spine. Fracture efficacy data are not yet available, although preliminary results are promising. The dose of nasal calcitonin for the treatment of established osteoporosis is 200 IU daily. The dose for prevention of postmenopausal osteoporosis has not yet been established. Nasal calcitonin may be analgesic to bone and of benefit in glucocorticoid-induced osteoporosis.

Objective: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy., Methods: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments., Results: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints., Conclusion: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.

Objective: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy., Methods: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments., Results: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints., Conclusion: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Objective: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy., Methods: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments., Results: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea., Conclusion: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

A superfamily of growth factor and cytokine receptors has recently been identified, which is characterized by four spatially conserved cysteine residues, a tryptophan-serine motif (WSXWS) in the extracellular domain, and a proline-rich cytoplasmic domain. The high affinity human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (hGM-CSFR) consists of two subunits, alpha (hGM-CSFR alpha) and beta (hGM-CSFR beta), both of which are members of the receptor superfamily. In this study, we prepared mutations in conserved amino acids of the receptor subunit necessary for GM-CSF binding (hGM-CSFR alpha) and analyzed mutant receptors for low affinity binding, internalization, and high affinity binding when complexed with the beta subunit. Mutations in the cytoplasmic domain did not affect GM-CSF binding or receptor internalization. Mutation of a single conserved serine residue within the WSXWS motif diminishes cell surface receptor expression but not ligand binding. Mutation of either the second or third conserved cysteine residue of hGM-CSFR alpha resulted in complete loss of low affinity binding; however, co-expression of the cysteine 2 mutant with hGM-CSFR beta yielded a high affinity receptor complex. Since neither the cysteine 2 mutant nor the beta subunit can bind ligand alone, this result suggests that hGM-CSFR alpha and hGM-CSFR beta exist in a preformed heterodimeric protein complex on the plasma membrane.

A 12-year-old patient with a severe traumatic brain injury developed heterotopic ossification (HO) with rapidly decreasing range of motion in multiple joints despite intensive passive range of motion exercises and the use of nonsteroidal antiinflammatory drugs (NSAIDs). His alkaline phosphatase was markedly elevated. Etidronate, 20mg/kg/d was used to control the ossification. After 7 months of continual etidronate use, the patient developed periarticular pain with widened growth plates, suggesting a rachitic syndrome. Serum laboratory panel including calcium, phosphorous, alkaline phosphatase, and vitamin D were normal. After 3 months off etidronate, radiological studies showed growth plate calcification, though not before development of bilateral slipped femoral capital epiphyses. Further improvement and resolution of all complications occurred 5 months after discontinuation of etidronate. Rachitic syndromes secondary to didronel use in a clinical setting has not been previously reported. Other possible causes for a rachitic syndromes were not present. Alternate treatments for children with or at risk for HO should be considered.

Vertebral compression fractures (VCFs) may be defined radiographically or as a clinical event. The prevalence of these fractures in women aged 50 and over has been estimated at 26% when defined as a reduction in vertebral height greater than 15%. Retrospective reviews of case records have shown a clinical detection rate of VCF in white women of 153/100,000 person years. Of these clinically detected VCFs, 84% were associated with pain. VCF may be defined as a clinical event characterised by loss of height and acute pain. The pain of acute fracture usually lasts 4 to 6 weeks with intense pain at the site of fracture. Chronic pain may also occur in patients with multiple compression fractures, height loss and low bone density but is probably due to structural changes or osteoarthritis. Radiographic VCF may not be symptomatic. The greater the deformity, the greater the likelihood of pain and disability. As height is lost, patients experience discomfort from the rib cage pressing downward on the pelvis. Patients develop a thoracic kyphosis, a lumbar lordosis, and a protuberant abdomen with prominent horizontal skinfold creases. The reduced thoracic space may result in decreased exercise tolerance and reduced abdominal space may give rise to early satiety and weight loss. Sleep disorders may also occur. Patients lose self esteem. Self care may become difficult. They are often depressed. They become fearful of further fracture. They have distorted body image and poor health perception. Patients with one vertebral fracture are at increased risk of peripheral fracture and further vertebral fracture. The aims of acute management are to reduce symptoms and mobilise the patient as quickly as possible.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied 70 patients (48 women and 22 men) with either rheumatic disease (n = 25) or lung disease (n = 45) who had been treated with glucocorticoids for at least 6 months (mean cumulative dose, 24.2 +/- 27.1 g of prednisone; mean current dose, 11.0 +/- 8.6 mg/d, mean duration of therapy, 8.1 years. We measured bone mineral density (BMD) of the hip (femoral neck) and spine (L2-L4) using dual-photon absorptiometry and BMD of the distal one third radius using single-photon absorptiometry. Compared with age-matched controls, the study population had decreased BMD of the spine (87.0%), hip (87.2%), and radius (90.6%). Current dose, cumulative dose, and duration of therapy were not correlated with BMD in the spine or hip in the total study population. The most significant correlations with low bone mass at the hip and spine were short height and low weight. There was a high incidence of hypercalciuria (30%) as compared with an age- and sex-matched control group (6.4%). Glucocorticoids are known to decrease vertebral and radial bone density. We conclude that glucocorticoids also decrease hip bone density as measured at the femoral neck. The high incidence of hypercalciuria may have implications for therapy of glucocorticoid-induced osteoporosis.

Thirty-five individuals with fibromyalgia (fibrositis), 22 of their physicians, and 49 rheumatologists on an Arthritis Foundation referral list rated the importance of 24 aspects of fibromyalgia treatment. These encompassed symptom control, psychosocial factors, information, and physical therapy. Respondents with fibromyalgia rated their satisfaction with the way each aspect of treatment had been managed by their physician, and each completed a health status questionnaire. Fibromyalgia patients viewed 8 of the 24 aspects of treatment as significantly more important than did their own physician, and 18 of the 24 as significantly more important than did area rheumatologists. Satisfaction with the way treatment had been managed was generally low. Some evidence suggested that patients' health status was affected positively by the extent to which their physician viewed certain aspects of treatment as important. The results are expected to be useful in the design of fibromyalgia education programs for both lay and health professional audiences.

Five young male heroin users presented with a syndrome resembling acute immune thrombocytopenic purpura. Although a viral, autoimmune, or toxic origin cannot be conclusively excluded at present, data are most consistent with the hypothesis that the thrombocytopenia was due to a drug-related immunologic mechanism that resulted in peripheral platelet destruction. Epidemiologic considerations suggest the common agent involved in their illnesses was present in the heroin they used. Although glucocorticoid therapy was followed by clinical recovery in four of the five patients (one was lost to follow-up), it is not certain that this represented a causal relation.

Mitogen induced cellular cytotoxicity (MICC) was noted to be markedly increased in patients with multiple myeloma as compared to normal controls and to patients with chronic lymphocytic leukemia (CLL). Enhanced MICC was present at various effector-to-target cell ratios and at several mitogen concentrations. Removal of adherent, phagocytic cells by carbonyl iron, glass wool, or rayon columns abolished the MICC response from the peripheral blood of both multiple myeloma patients and normal controls. Thus, the effector cell mediating MICC may be monocytic in origin and closely resembles the suppressor cell for immunoglobulin synthesis described in patients with multiple myeloma. Our data suggest that the MICC assay with chicken red blood cells as targets may provide a convenient method for identifying pathologic conditions where this cytotoxic effector cell population plays an active role.