Bone status in glucocorticoid-treated men and women.

UNLABELLED: We recorded the results of areal bone mineral density (aBMD) and microarchitecture of the bone measured by trabecular bone score (TBS) in 416 glucocorticoid-treated men and women aged 40 years and older with or without fracture to 1104 controls. TBS better discriminated those with fracture compared to aBMD. These differences were the greatest in men. INTRODUCTION: The aim of this study is to evaluate glucocorticoid (GC)-induced effects on areal bone mineral density (aBMD) and bone microarchitectural texture measured by trabecular bone score (TBS). METHODS: TBS and aBMD were evaluated at L1-L4 postero-anterior (PA) spine by dual X-ray absorptiometry (DXA) in 1520 men and women aged 40 years and over. Four hundred sixteen subjects who received GCs (≥5 mg/day, for ≥3 months) were matched with 1104 sex-, age-, and BMI-matched control subjects. Clinical data, osteoporotic fractures (OPF), and dietary habits were documented in the medical report. RESULTS: GC-treated patients were characterized by a significant decrease of TBS (1.267 vs. 1.298, p < 0.001) compared with control-matched subjects while no change in BMD was observed at any sites. These decreases were even more pronounced when fracture status was taken into account (1.222 vs. 1.298, p < 0.001). The odds ratio (OR) for TBS was 1.44 (1.095-1.89) for OPF, whereas no association was found for BMD at any sites (all p > 0.3). A similar effect on microarchitecture measured by TBS was seen by the presence of fracture as by the use of glucocorticoids. An influence on TBS by sex was also noted with a decrease in TBS of greater magnitude in men. CONCLUSIONS: GC-treated individuals have a significant deterioration of bone microarchitectural texture as assessed by TBS which is more marked in those with OPF and in men. TBS seems to be more sensitive than aBMD for GC-related fracture detection and should be a good surrogate indicator of bone health in such secondary osteoporosis.

"Evidence-based" or "logic-based" medicine?

Low trauma fractures are the cardinal manifestation of osteoporosis. Their occurrence supersedes bone mineral density in deciding whether specific therapy is warranted. We therefore disagree with the notion that a densitometric threshold for treatment should be applied to patients over age 50 who suffer low trauma distal radius fracture.

Factors related to the use of bone densitometry: survey responses of 494 primary care physicians in New England.

Large population-based surveys have shown that approximately 30% of people over age 65 years have osteoporosis and that 17% of the population over 65 years will sustain a fracture during their lifetime. Many people with osteoporosis are never being evaluated even though effective treatments are available. We examined why primary care physicians order few bone mineral density scans. We conducted a cross-sectional survey of primary care physicians practicing in any of the six New England states. Target physician specialties included internal medicine, general practitioners/family physicians, and obstetrician-gynecologists who had a facsimile number listed with the American Medical Association. Demographics, practice characteristics, use of bone densitometry, and attitudes regarding osteoporosis, bone densitometry and health maintenance were assessed by questionnaire. Twelve percent (n=494) of the physicians responded to the questionnaire. Respondents were similar to non-respondents with respect to years of practice, training and geographical state, though they were more likely to be female (p < or =0.05). Respondents had a mean age of 51 years, and 51% were trained in internal medicine, 25% in general practice/family practice and 24% in obstetrics-gynecology. The mean number of self-reported bone densitometry referrals per month was 10+/-11, and 25% of respondents reported that they referred fewer than 4 patients per month. In adjusted logistic models, factors significantly associated with referring fewer than 4 patients per month were: training in internal medicine (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9) or general practice/family practice (OR 2.6, 95% CI 1.3-5.2) versus obstetrics-gynecology; practicing in an urban setting (OR 2.5, 95% CI 1.3-4.9) or rural/small town setting (OR 2.2, 95% CI 1.2-4.1) versus a suburban setting; spending less than 50% of professional time in patient care (OR 4.0, 95% CI 1.7-9.5); seeing the lowest proportion of postmenopausal women (OR 2.5., 95% CI 1.2-5.3); the belief that calcium and vitamin D are adequate to treat osteoporosis (OR 2.1, 95% CI 1.0-4.5); and the belief that osteoporosis treatment should not be based on bone density results (OR 3.2, 95% CI 1.7-6.1). Potentially modifiable physician beliefs and a number of practice characteristics are associated with low referral rates for bone densitometry. Educational strategies aimed at improving the use of bone density testing should consider these factors.

Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis.

OBJECTIVE: To determine the effects of low dose methotrexate (MTX) on bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: We examined the relationship between BMD and disease modifying antirheumatic drug (DMARD) use with data from a prospective, randomized, placebo controlled trial assessing the effects of calcium and vitamin D3 supplementation on BMD of patients with RA. Measurements of BMD of the lumbar spine and femoral neck were performed at baseline and at yearly followup visits over 3 years. RESULTS: Information about DMARD use and BMD was available for 133 patients at baseline, and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non-MTX treated patients were similar at the start of the study. At the end of 3 years of followup, there was no significant differences in the change in BMD of the femoral neck and lumbar spine in MTX and non-MTX treated patients, in general. However, patients treated with prednisone > or = 5 mg/day plus MTX had greater loss of BMD in the lumbar spine than patients treated with a similar dose of prednisone without MTX (difference -8.08% over 3 years; p = 0.004). CONCLUSION: At the end of 3 years, low dose MTX use was not associated with change in femoral neck or lumbar spine BMD in patients who were not treated with corticosteroids. However, among patients treated with prednisone > or = 5 mg/day, combined treatment with MTX and prednisone was associated with greater bone loss in the lumbar spine than treatment with prednisone without MTX.

Prevalence of pulmonary hypertension in limited and diffuse scleroderma.

STUDY OBJECTIVES: To characterize the prevalence of undiagnosed pulmonary hypertension in patients with limited and diffuse scleroderma. DESIGN: Prospective cross-sectional study. SETTING: University-based outpatient clinic. PATIENTS: Thirty-four consecutive patients with limited (n = 29) or diffuse (n = 5) scleroderma but without the clinical diagnosis of pulmonary hypertension. MEASUREMENTS AND RESULTS: All patients had 12-lead ECGs and two-dimensional and Doppler echocardiograms. The pulmonary artery systolic pressure (PAs) was calculated as the sum of the Doppler transtricuspid pressure gradient and the right atrial pressure as estimated by the caval respiratory index. Thirty-three patients (97%) had adequate spectral signals of tricuspid regurgitation. The velocity of tricuspid regurgitation ranged from 1.6 to 4.5 m/s. The calculated PAs ranged from 15 to 95 (mean +/- SD = 30 +/- 14 mm Hg). Twelve patients (35% of the total cohort) had pulmonary hypertension defined as PAs of 30 mm Hg or greater. CONCLUSIONS: Undiagnosed elevation of PAs is common in patients with scleroderma. Noninvasive assessment of PAs can be performed accurately in most patients independent of clinical signs of pulmonary hypertension. If successful treatment strategies are identified, it may be possible to identify patients early in the development of pulmonary hypertension and intervene before significant end-organ damage occurs.

Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists. OBJECTIVE: To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use. DESIGN: 2-year randomized, double-blind, placebo-controlled trial. SETTING: University outpatient-care facility. PATIENTS: 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d). INTERVENTION: Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo. MEASUREMENTS: Bone mineral densities of the lumbar spine and femur were determined annually. RESULTS: Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids. CONCLUSION: Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.

Effects of low dose corticosteroids on the bone mineral density of patients with rheumatoid arthritis.

OBJECTIVE: To assess the effect of low doses of corticosteriods on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: A cross sectional study of BMD as measured by dual photon x-ray of the femoral neck and lumbar spine (lateral view) in 139 patients with RA followed in a university setting. RESULTS: The mean daily dose of prednisone taken by the study group was 4.15 mg/day. Patients receiving daily doses of prednisone between 1 to 4 mg/day had similar BMD to patients who were not receiving corticosteroids, but patients taking 5-9 mg/day and those taking > 10 mg/day had significantly lower BMD of the lumbar spine (84.28 and 80.51% of controls, respectively) than patients who received 1-4 mg/day (99.16% of controls). The effect of corticosteroids remained significant when other risk factors such as disease severity, disease duration, functional class, and activity level were controlled for. No significant relationship between prednisone dose and BMD of the femoral neck was seen at the low doses studied. CONCLUSION: Low dose corticosteroid use has a significant effect on BMD of the lumbar spine.

Toxic megacolon associated with methotrexate therapy.

We describe the case of a patient with psoriasis who developed severe colitis, with toxic megacolon, after a course of treatment with methotrexate. The duration of her colitis, which was eventually resolved by using conservative measures, was far greater than that of other drug-related complications, which included bone marrow depression, jaundice, and renal failure. The literature pertaining to this rare manifestation of methotrexate toxicity is reviewed. A prolonged illness and relative sparing of the distal colon appear to be characteristic of this form of colitis.

Correlation of disease activity in systemic necrotizing vasculitis with immune complexes.

Ninety-four sera from 23 patients with necrotizing vasculitis of the polyarteritis nodosa (PAN) type were examined for immune complexes by polyethylene glycol (PEG) precipitation. The presence of immune complexes in serum specimens was positively correlated with the presence of active disease in PAN (p less than .001). These complexes predicted active disease 93% of the time and their absence predicted a period of inactivity 54% of the time. The presence of hepatitis B markers, Clq immune complexes, rheumatoid factor, or low complement levels did not correlate with active disease. In 9 patients in whom serial specimens were tested for immune complexes there was a positive association of immune complexes and active PAN.

Immunosuppressive and corticosteroid therapy of polyarteritis nodosa.

The clinical manifestations, treatment and survival of 64 patients with polyarteritis nodosa seen from 1955 to 1977 were evaluated. In general, the patients had multisystem involvement. No patient with cutaneous vasculitis alone was accepted into the study. The clinical diagnosis was confirmed by biopsy in 34 patients, by autopsy in 13 and by angiography in 10. The patients were treated at the discretion of the physicians responsible for their care. Eight of the 64 patients received only supportive therapy (group 1), 34 received corticosteroids alone (group 2), and 22 received both corticosteroids and an immunosuppressive agent (group 3). Five patients in group 2 and one patient in group 3 were excluded from survival studies because of insufficient length of therapy. Patients in the three treatment groups were very similar with respect to 18 clinical and laboratory variables. Median survival times for the three groups were three months, 63 months and 149 months, respectively; 5 year survival rates were 12 per cent, 53 per cent and 80 per cent (p less than 0.05). Despite difficulty in precisely defining polyarteritis nodosa, the data suggest a better prognosis for treated patients than has previously been appreciated, with improvement in outcome when an immunosuppressive agent is added to corticosteroid therapy.