Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?

OBJECTIVE—To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids.
PATIENTS AND METHODS—47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months.
RESULTS—After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p<0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: −2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p<0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: −2.5% (95% CI: −6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: −4.0% (95% CI: −6.6% to −1.4%; p<0.01). The difference between the groups was not significant: +1.5% (95% CI: −3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups.
CONCLUSION—The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.

     

Clinical experience with etidronate in osteoporosis

Summary Clinical experience with cyclical etidronate for the treatment of osteoporosis was reviewed in 69 consecutive patients. Six patients stopped treatment either due to adverse effects (5) or the decision to take hormone replacement therapy (HRT) (1). Bone mineral density (BMD) measurements using dual energy X-ray absorptiometry (DXA) were obtained in 63 patients (33 with spinal osteoporotic fractures and 30 with osteopenia) before and 1 year after treatment. BMD increased by an average of 4.50% (p<0.001) in the lumbar spine (range +14% to –12%) and 5.5% (p<0.01) at Ward's triangle (range +31% to –13%) while there was no significant change at the femoral neck (range +11% to –12%) and greater trochanter (range +12% to –15%). Significant rises in BMD were found at the lumbar spine and Ward's triangle in both osteoporotic and osteopenic groups. Of patients analysed after 1 year, 83% had an increased bone mass at the lumbar spine and 55% at the femoral neck.We conclude that there is a whide variation in the bone mass response to cyclical etidronate therapy, and in a minority of patients bone mass does not increase. For the majority of osteoporotic patients, however, we confirm the efficacy and tolerability of cyclical etidronate for the preservation of bone mass over 1 year in a clinical setting.     

Timing of cyclical etidronate

OBJECTIVE: The importance of the timing of the etidronate component of cyclical etidronate was investigated in a study examining changes in lumbar spine BMD. METHODS: Seventy patients who had been taking cyclical etidronate for at least 1 year and who had baseline BMD studies and a further scan 1 year later were mailed a questionnaire asking about the time of day they took the etidronate component. Replies were received from 52 patients who were of average age 67.5 years (SD 6) and had been on therapy for an average of 2.7 years. Patients were divided into 3 groups according to when they took etidronate: Group A--Fasting on waking, Group B--During the day, and Group C--Before retiring to bed or during the night. All patients except 2 claimed to avoid food and drink apart from water for 2 hours either side of taking etidronate. RESULTS: The mean increases in BMD over 1 year were 3.1% group A, -0.14% Group B, and 5.4% Group C and the total change over duration of use were 5.6%, 1.2% and 7.5%, respectively. There were significant differences (P < 0.05) between group B and the other 2 groups at 1 year and over 2.7 years. CONCLUSION: We conclude that the 2-hour rule may be insufficient for taking etidronate during the day and that the etidronate component of cyclical etidronate is best taken in the early morning or late evening/at night.     

Longterm effect of intermittent cyclical etidronate therapy on corticosteroid-induced osteoporosis in Japanese patients with connective tissue disease: 7-year followup

OBJECTIVE: To determine the efficacy and safety of intermittent cyclical etidronate therapy of up to 7 years for corticosteroid-induced osteoporosis. METHODS: One hundred two Japanese patients who originally participated in a 3-year prospective randomized study were enrolled into an open-label followup study. All patients had received > 7.5 mg of prednisolone daily for at least 90 days before entry into the original study and were randomly assigned to 2 treatment arms: E, those receiving etidronate disodium (200 mg per day) for 2 weeks together with 3.0 g of calcium lactate and 0.75 microg of alphacalcidol daily; and C, controls receiving only the latter. Endpoints included changes from baseline in bone mineral density (BMD) of the lumbar spine and the rate of new vertebral fractures. RESULTS: The mean (+/- SD) lumbar spine BMD had increased by 5.9% +/- 8.8% (p = 0.00007) and 2.2% +/- 5.8% (p = 0.013) from baseline after 7 years in groups E and C, respectively. This improvement in BMD in group E was significantly better than in group C (p = 0.02). The frequency of new vertebral fractures was lower in group E, resulting in reduction of the risk of such new fractures by 67% at year 7 (odds ratio 3.000; 95% confidence interval, 0.604 14.90; p = 0.18). There were no severe adverse events in group E during our study. CONCLUSION: Our results indicate that longterm (up to 7 years) intermittent cyclical etidronate therapy is safe and effective for prevention and treatment of corticosteroid-induced osteoporosis in patients with connective tissue diseases.     

The prevention of corticosteroid-induced bone loss with intermittent cyclical etidronate.

A prospective, randomised, double-blind, placebo controlled primary prevention trial was undertaken in 28 patients commencing low to moderate doses of corticosteroids for the first time. Patients were randomised to intermittent cyclical etidronate (400 mg daily for 2 weeks) and calcium (500 mg daily for 11 weeks) or intermittent cyclical placebo with calcium. After 52 weeks of treatment, lumbar spine BMD increased by 1.8% in the etidronate group, while it decreased by 3.7% in the placebo group. The differences in bone loss rate were statistically significant (p<0.01) at both 6 and 12 months. Similar trends were observed at the proximal femur, but differences were not statistically significant. These results suggest that intermittent cyclical etidronate therapy is effective in the primary prevention of corticosteroid-induced bone loss at the lumbar spine.     

36 month intermittent cyclical etidronate treatment in patients with established corticosteroid induced osteoporosis.

OBJECTIVE: To determine the longterm safety and efficacy of etidronate therapy in patients in whom corticosteroid induced bone loss has already occurred. METHODS: We performed a 36 month observational cohort study in which all data were obtained from Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. The etidronate group consisted of 24 patients who received 400 mg of etidronate disodium for 14 days, followed by 76 days of calcium carbonate (500 mg of elemental calcium), repeated every 3 mo; the control group included 37 patients who received calcium carbonate 500 to 1000 mg daily. Outcome measurements included changes within groups from baseline and differences between groups in the bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter at 12, 24, and 36 months. The incidence of vertebral fractures was also determined. RESULTS: Etidronate therapy resulted in a meaningful percentage increase from baseline in lumbar spine BMD, primarily during the first 24 months of treatment, and this increase was sustained for the remainder of the 36 month study period (5.2%; p = 0.016). Analysis of covariance revealed a significant percentage difference (SD) between groups in lumbar spine BMD at 12 [5.5 (13.5) percent; p = 0.003] and 24 months [6.0 (17.4) percent; p = 0.011] in favor of the etidronate group. After 3 years of therapy, one patient (4%) experienced one vertebral fracture in the etidronate group, whereas 3 patients (8%) experienced 5 vertebral fractures in the control group. CONCLUSION: Etidronate treatment administered for 36 months reversed lumbar spine bone loss, and appeared to be safe in patients with established corticosteroid induced osteoporosis.     

Bone mineral density and nutritional status in children with chronic inflammatory bowel disease

Background—Osteoporosis has been reported inadult patients with inflammatory bowel disease.
Aims—To evaluate bone mineral density (BMD),nutritional status, and determinants of BMD in children withinflammatory bowel disease.
Patients—Fifty five patients (34 boys and 21 girls, age range 4-18) were studied; 22 had Crohn's disease and 33 ulcerative colitis.
Methods—Lumbar spine and total body BMD, and bodycomposition were assessed by dual energy x rayabsorptiometry (DXA). Results were expressed as standard deviationscores (SDS). Lean body mass was also assessed by bioelectricalimpedance analysis (BIA). Yearly measurements during two years wereperformed in 21patients.
Results—The mean SDS of lumbar spine BMD andtotal body BMD were significantly lower than normal (−0.75 and−0.95, both p<0.001). Height SDS and body mass index SDS were alsodecreased. The decrease in BMD SDS could not be explained by delay inbone maturation. The cumulative dose of prednisolone correlatednegatively with lumbar spine BMD SDS (r=−0.32, p<0.02).Body mass index SDS correlated positively with total body BMD SDS(r=0.36, p<0.02). Patients with Crohn's disease hadsignificantly lower lumbar spine and total body BMD SDS than patientswith ulcerative colitis, even after adjustment for cumulative dose ofprednisolone. In the longitudinal data cumulative dose of prednisolonebetween the measurements correlated negatively with the change inlumbar spine and total body BMD SDS. Lean tissue mass measured by DXAhad a strong correlation with lean body mass measured by BIA(r=0.98).
Conclusions—Children with inflammatory boweldisease have a decreased BMD. Children with Crohn's disease have ahigher risk of developing osteopaenia than children with ulcerativecolitis. Corticosteroid therapy and nutritional status areimportant determinants of BMD in these patients.

Keywords:bone mineral density; inflammatory bowel disease; children; nutritional status; corticosteroid treatment; bodycomposition

     

Prevention of early postmenopausal bone loss with cyclical etidronate

Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss. The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early postmenopausal women. One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year, randomised, placebo-controlled, double-blind trial. Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline. Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen cross-links (deoxypyridinoline and pyridinoline) were measured at the same time points. Seventy-seven women completed the study. At the end of the treatment period, the mean bone mineral density change from baseline in the treated group was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively, compared to -1.49 and -2.22 in the control group. Overall, there was a significant difference between the two groups at both these sites (p=0.01 and 0.001, respectively). No significant differences between the groups were demonstrated at the greater trochanter or Ward's triangle. The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women. It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy.     

Effect of intermittent cyclical etidronate therapy on corticosteroid induced osteoporosis in Japanese patients with connective tissue disease: 3 year followup

OBJECTIVE: A 3 year prospective randomized study was conducted to clarify the efficacy of intermittent cyclical etidronate therapy on corticosteroid induced osteoporosis. METHODS: A group of 102 Japanese patients were enrolled, each taking > 7.5 mg of prednisolone daily for at least 90 days. Patients were randomly divided into 2 treatment groups: Group E (etidronate) took 200 mg etidronate disodium per day for 2 weeks with 3.0 g calcium lactate and 0.75 microg alphacalcidol daily; Group C (control) took 3.0 g calcium lactate and 0.75 microg alphacalcidol daily. Outcome measurements included changes from baseline in bone mineral density (BMD) of the lumbar spine and the rate of new vertebral fractures at 48 and 144 weeks. RESULTS: The mean (+/- SD) lumbar spine BMD increased 3.7 +/- 5.6% (p < 0.01) and 1.5 +/- 4.1% (NS) from baseline at 48 weeks and 4.8 +/- 6.9% (p < 0.005) and 0.4 +/- 5.0% (NS) from baseline at 144 weeks in Group E and Group C, respectively. The improvement of BMD in Group E was significantly greater than in Group C at 144 weeks (p < 0.01). In 3 subgroups, men and premenopausal and postmenopausal women, the postmenopausal women showed the greatest improvement. Mean percentage change in this subgroup was 10.1 +/- 8.0% and 1.35 +/- 6.4% in Group E and Group C, respectively. We noted that 2 patients in Group C had new vertebral fractures, whereas no fractures were observed in Group E. CONCLUSION: These results indicate that intermittent cyclical etidronate therapy is effective for the prevention and treatment of corticosteroid induced osteoporosis in patients with connective tissue diseases.     

Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation

OBJECTIVE Our clinical practice has been to offer treatment with cyclical disodlum etidronate and high dose calcium supplements (1500–1600 mg/day) to ail female patients with osteoporosis who are unable or unwilling to take hormone replacement therapy (HRT), and male osteoporotics. In a retrospective study we compared the effect of this treatment on measures of bone mineral over a 12-month period in women wlth post-menopausal and secondary osteoporosis. We also assessed its effects in 10 male osteoporotics. DESIGN A retrospective analysis of 83 consecutive patients with osteoporosis who completed 12 months of treatment with disodlum etldronate and calcium and who had a dual energy X-ray absorptiometry (DEXA) scan at baseline and foilowing 12 months of therapy. PATIENTS The study Included 73 women (45 post-meno-pausal and 28 secondary osteoporotics) and 10 men with established osteoporosis as shown by spinal and femoral bone mineral densities (BMD) > 2 standard deviations (SD) below young normals, and radioiogical evidence of osteoporosis. MEASUREMENTS Each patient had routine biochemistry at baseline, an X-ray of thoracic and lumbar spine and a DEXA scan of lumbar spine (L2-L4) and femoral neck. The DEXA scan was repeated following 12 months of therapy. RESULTS There was no difference between increase in spinal BMD in the post-menopausal (5·7%) versus secondary osteoporotic group (6·7%). There was a significant increase in spinal BMD at 12 months in the 10 male osteoporotics (9·0%, P < 0·01). No overall change in femoral neck BMD was noted. CONCLUSIONS Cyclical disodium etidronate given with hlgh dose calcium supplements is equally effective in increasing spinal bone mineral density in post-menopausal and secondary osteoporosis. It also results in a significant rise In spinal bone mineral density in male osteoporotics. Whether this produces a reduction in fracture rates is unknown.     

Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies

STUDY DESIGN—Cross sectional.
RESEARCH QUESTIONS—(a) Is any clinical variable of ankylosing spondylitis (AS) associated with the presence of ossification of the posterior longitudinal ligament (OPLL)? and (b) Is OPLL present in patients with AS from different geographical or genetic backgrounds?
METHODS—Three groups were assembled: (1) a prospective group of 103 consecutive AS patients from two community based rheumatology clinics from Guadalajara, who were evaluated using: a questionnaire with disease characteristic variables; clinical assessment by a neurologist; lateral radiographic views of the cervical spine and somatosensory evoked potentials (SSEP). (2) Fifty one spondyloarthropathies (SpA) patients from Mexico city whose cervical spine films were retrospectively reviewed. (3) Thirty nine AS patients from Edmonton, Canada whose cervical spine films were retrospectively reviewed and compared with 72 controls.
RESULTS—Group 1: 74% of the 103 patients were men and 86% were HLA-B27 positive. The mean age was 35 years, and mean (SD) disease duration 10 (8) years. OPLL was reported in 16 patients (15.5%; 95%C I 9, 22). OPLL was statistically associated with older age (p=0.001), longer disease duration (p=0.001), clinical myelopathy (p=0.03), worst functional index (p=0.042), restricted axial movement measurements (all p<0.001), radiological sacroiliitis (p<0.001 for linear association), osteitis pubis (p=0.009), hip involvement (p=0.006 for linear association), and abnormal SSEP (p=0.008). Group 2: 92% of 51 patients were men; the mean age was 30 years and the mean (SD) disease duration 11 (7) years. OPLL was reported in 15 (29%, 95%CI 17, 41) patients (nine AS, two psoriatic arthritis, three juvenile AS, and one Reiter's syndrome). Group 3: 95% of the 39 patients were men; the mean of age was 46 years and disease duration of 18 (10) years. OPLL was reported in nine (23%; 95%CI 10, 36) patients, including one with psoriatic arthritis, and two with Crohn's disease. OPLL was observed in two of the control group.
CONCLUSIONS—The prevalence of OPLL in AS and SpA is higher than previously recognised and seems to be associated with variables identifying more severe axial disease.

Keywords: ankylosing spondylitis; ossification of the posterior longitudinal ligament; psoriatic arthritis; Reiter's syndrome     

The impact of plant-based diets on female bone mineral density: Evidence based on seventeen studies

Background:An increase in awareness of plant-based diets has brought forth numerous studies on bone mineral density (BMD). The present systematic review and meta-analysis was designed to compare the effect between plant-based diets and omnivores on female BMD.Methods:We searched the Cochrane Library, PubMed, EMBASE, and Web of Science and up to July 1, 2020. Mean difference (MD) with its 95% confidence interval (CI) was estimated to compare the outcomes of the groups. We compared BMD at the lumbar spine, femoral neck and whole body respectively between plant-based diets and omnivores. In addition, we performed subgroup analyses according to different clinical characteristics for further exploration. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2.Results:A total of 17 cross-sectional studies including 13,888 patients were identified for the present meta-analysis. Our pooled result indicated that population with plant-based diets had lower BMD than omnivores at the lumbar spine (MD −0.03; 95% CI −0.04 to −0.02; P < .0001), femoral neck (MD −0.04; 95% CI −0.05 to −0.03; P < .00001) and whole body (MD −0.04; 95% CI −0.06 to −0.01; P = .01), respectively. Further exploration indicated that especially females with plant-based diets experienced significantly lower BMD at lumbar spine (MD −0.03; 95% CI −0.04 to −0.02; 3173 pts), femoral neck (MD −0.04; 95% CI −0.05 to −0.03; 10,656 pts) and whole body (MD −0.05; 95% CI −0.10 to −0.00; P = .04). In addition, we performed subgroup analyses and found lower BMD at lumbar spine and femoral neck in both vegetarians and vegans.Conclusions:The present meta-analysis indicated that plant-based diets may be correlated with lower BMD of women when compared with omnivore population. However, this does not diminish the fact that a plant-based diet can be a harmful option to the overall bone health of population and more prospective researches are needed to clear the impact of plant-based diets on bone health.     

A pooled data analysis on the use of intermittent cyclical etidronate therapy for the prevention and treatment of corticosteroid induced bone loss

OBJECTIVE: To conduct a pooled data analysis in a group of patients defined by sex, menopausal status, and underlying disease in order to examine the effect of intermittent cyclical etidronate in the prevention and treatment of corticosteroid induced osteoporosis. METHODS: We selected 5 randomized, placebo controlled studies that examined the efficacy of intermittent cyclical etidronate therapy in which the raw data were available for analysis. Three were prevention studies and 2 treatment studies. The primary outcome was the difference between treatment groups in the percentage change from baseline in lumbar spine bone density. Secondary outcomes included the difference between treatment groups in the percentage change from baseline in femoral neck and trochanter bone density, and vertebral fracture rates. RESULTS: Results are separately pooled for the prevention and treatment studies. The prevention studies had significant mean differences (95% CI) between groups in mean percentage change from baseline in lumbar spine, femoral neck, and trochanter bone density of 3.7 (2.6 to 4.7), 1.7 (0.4 to 2.9), and 2.8% (1.3 to 4.2) after one year of treatment, in favor of the etidronate group. The treatment studies displayed a mean difference between groups in mean percentage change from baseline in lumbar spine bone density of 4.8 (2.7 to 6.9) and 5.4% (2.5 to 8.4) after one and 2 years of therapy. In the prevention studies, a reduced fracture incidence was observed in the etidronate group compared with the placebo group (relative risk 0.50; CI 0.21 to 1.19). CONCLUSION: Etidronate therapy was effective in preventing bone loss in the prevention studies and in preventing or slightly increasing bone mass in the treatment studies. A fracture benefit was observed in postmenopausal women treated with etidronate in the prevention studies.     

Incidence, recurrence, and case fatality rates for myocardial infarction in southwestern France, 1985 to 1993

OBJECTIVE—To assess the impact of incidence, recurrence, and case fatality rates for myocardial infarction on coronary heart disease mortality in southwestern France between 1985 and 1993.
DESIGN—Toulouse-MONICA myocardial infarction register.
SETTINGS AND PATIENTS—All subjects aged 35 to 64 years living in the French department of Haute-Garonne.
INTERVENTIONS—All coronary artery disease events between 1985 and 1993.
MAIN OUTCOME MEASURES—7210 events collected by the register between 1985 and 1993.
RESULTS—In men, adjusted attack, total, and out of hospital mortality decreased by 2% (95% confidence interval (CI), −3.8% to −0.1%), 6.2% (95% CI −8.4% to −4.0%), and 4.2% (95% CI −7.0% to −1.5%) a year, respectively (p < 0.05). Incidence and recurrence rates decreased by 2% (95% CI −4.1% to −0.1%, p < 0.05) and 1.9% (95% CI −5.9% to 2.2%) a year (NS). In women, attack, total, and out of hospital mortality decreased by 1.7% (95% CI −5.2% to 1.8%), 4.8% (95% CI −9.6% to 0.1%), and 2.6% (95% CI −9.4% to 4.1%) a year, respectively; incidence decreased by 2% (95% CI −6.5% to 2.5%) and recurrence increased by 1.4% (95% CI −9.8% to 12.6%) a year (all NS). In men, total, incident, and recurrent 28 day case fatality decreased by 3.8% (95% CI −4.8% to −2.8%), 3.2% (95% CI −4.1% to −2.3%), and 6.4% (95% CI −9.5% to −3.3%) a year, respectively (p < 0.05). For women, the corresponding decreases were 3.3% (95% CI −6.1% to −0.6%), 3.3% (95% CI −13.2% to 6.6%), and 11.7% (95% CI −24.6% to 1.3%) a year, but only the decrease in total 28 day case fatality reached significance. In both sexes, the reduction in case fatality contributed nearly 70% of the decrease in myocardial infarction mortality.
CONCLUSIONS—In southwestern France, the decrease in myocardial infarction mortality mainly reflects improvements in acute management rather than prevention.


Keywords: myocardial infarction; case fatality     

The clinical benefits to bone mineral density were shown by cyclical oral etidronate administration in steroid induced osteoporosis]

PURPOSE: To compare the bone-mass effects of intermittent cyclic etidronate administration in patients of various rheumatic disease patients with corticosteroid-induced osteoporosis. PATIENTS AND METHODS: We evaluated bone mineral density (BMD) of lumbar spine in 34 female patients (mean age: 46.4 +/- 13.7 y. o. 17-71) treated with long term corticosteroid (> 6 months). Eighteen patients cyclically received etidronate orally (400 mg or 200 mg etidronate daily for 2 weeks, followed by 10-12 weeks drug-free periods). Twelve in these 18 patients received 400 mg (group A) and another 6 patients were treated with 200 mg/day (group B). Sixteen patients free from etidronate administrations were analysed as a control group. RESULTS: Cyclical etidronate therapy showed significant increase in BMD. The BMD of lumbar spine increased from 0.760 +/- 0.10 g/cm 2 to 0.783 +/- 0.11 g/cm 2 (%change from baseline 2.91 +/- 2.56%/year) in group A treated patients after 12 months. Reduced BMD (%change from baseline 1.55 +/- 2.48%) was observed in 16 control group patients (P < 0.0012). The BMD in group A was significantly high compared to group B or control after the etidronate treatment. In 7 of group A, BMD increased significantly on 6 months but no more significant increase was shown on 12 months compared to the value on 6 months. On the other hand the BMD tend to increased for after 2 years in intermittent cyclic etidronate treatment in 8 cases of group A. There were no adverse effects and abnormal laboratory data related to the administration of etidronate. Although only 2 cases of group A showed the findings of compression fracture before the study, but no new compression fracture appeared in any group during this study. CONCLUSION: It was shown that cyclical etidronate therapy is effective for steroid induced osteoporosis.     

Growth in infancy and bone mass in later life

OBJECTIVE—To examine the association between weight in infancy and bone mass during the seventh decade of life in a population based cohort for which detailed birth and childhood records were preserved.
METHODS—189 women and 224 men who were aged 63-73 years and were born in East Hertfordshire underwent bone densitometry by dual energy x ray absorptiometry. Measurements were also made of serum osteocalcin and urinary excretion of type 1 collagen cross linked N-telopeptide.
RESULTS—There were statistically significant associations between weight at 1 year and bone mineral content (but not bone mineral density) at the spine (P < 0.02) and femoral neck (P < 0.01) among women, and spine (P < 0.03) among men. Although serum osteocalcin was negatively correlated with bone mineral density at both sites among men and women, infant weight was not significantly associated with either biochemical marker of bone turnover.
CONCLUSIONS—These data confirm our previous observations that growth in infancy is associated with skeletal size in adulthood, and suggest that skeletal growth may be programmed during intrauterine or early postnatal life.

     

Calcium,vitamin D and etidronate for the prevention and treatment of corticosteroid-induced osteoporosis in patients with rheumatic diseases

INTRODUCTION: Long-term glucocorticoid therapy, a major risk factor for the development of osteoporosis, is often necessary in chronically ill patients. At present there are no generally accepted guidelines for the prevention or treatment of steroid-induced osteoporosis. METHODS: In an open prospective study we investigated 99 patients with chronic rheumatic diseases receiving > or = 5 mg/day of prednisolone or the equivalent for at least one year. The objective was to identify osteoporosis risk factors in addition to glucocorticoid therapy and to evaluate the efficacy of prevention with calcium/vitamin D (group 1--patients with osteopenia) and treatment with cyclical etidronate (group 2--patients with osteoporosis). Biochemical markers of bone turnover, clinical parameters and bone mineral density (BMD) were measured. RESULTS: Increasing age and postmenopausal status were associated with more advanced manifestations of steroid-induced osteoporosis (p < 0.05). One year after the start of therapy parameters of bone metabolism increased significantly in group 1, while BMD did not change. In group 2, lumbar spine BMD increased significantly (p < 0.05) whereas femoral neck BMD and bone metabolism parameters remained constant. The intensity of back pain decreased in both groups (p < 0.05). There were fewer new fractures in group 2 than in group 1. CONCLUSION: Treatment with etidronate is effective in patients with glucocorticoid-induced osteoporosis.     

Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults

OBJECTIVE—To define the pattern of disease expression in patients with childhood onset systemic lupus erythematosus (SLE).
METHODS—Prospective analysis of clinical manifestations and immunological features of 34 patients in whom the first manifestations appeared in childhood from a series of 430 unselected patients with SLE.
RESULTS—Thirty one (91%) patients from the childhood onset group were female and three male (9%) (ratio female/male, 10/1, with no difference compared with the adult onset group). Mean age of this group at disease onset was 11 years (range 5-14) compared with 32 years (15-48) for the remaining patients. The childhood onset patients more often had nephropathy (20% v 9% in adult onset SLE, p=0.04; OR:2.7; 95%CI:1.1, 7), fever (41% v 21%, p=0.006; OR:2.6, 95%CI:1.2, 5.7), and lymphadenopathy (6% v 0.5%, p=0.03, OR: 12.3, 95%CI: 1.2, 127.6), as presenting clinical manifestations. During the evolution of the disease, the childhood onset patients had an increased prevalence of malar rash (79% v 51%, p=0.002; OR:3.7; 95%CI:1.5, 9.5) and chorea (9% v 0%, p<0.0001). This group exhibited a higher prevalence of anticardiolipin antibodies (aCL) of the IgG isotype when compared with the remaining patients (29% v 13%, p=0.017; OR:2.9, 95%CI:1.2, 6.8). No significant differences were found among the other antibodies between the two groups. Childhood onset patients more often received azathioprine (15% v 6%, p=0.00004; OR:11.2; 95%CI:2.8, 44.9) but no differences were detected between the groups concerning side effects or drug toxicity.
CONCLUSIONS—The presentation and the clinical course of SLE varied in this series of 430 patients depending on their age at disease onset. Nephropathy, fever, and lymphadenopathy were more common in childhood onset patients as presenting clinical manifestations, while malar rash, chorea, and detection of IgG aCL were more common during the evolution of the disease.

Keywords: systemic lupus erythematosus; childhood; age     

The use of cyclical etidronate in osteoporosis: changes after completion of 3 years treatment

An open study over 4 yr has been conducted to determine the efficacy of cyclical etidronate treatment in patients from the community, with osteoporosis and in those at risk who attended an osteoporosis clinic; and to clarify whether bone remodelling returns to baseline values and bone mass is maintained after completion of a 3 yr course of treatment. One hundred and fifteen female patients, with and without osteoporotic fractures (n = 62 and 53, respectively), who were unsuitable for, or declined, hormone replacement therapy, received 3 yr cyclical etidronate treatment (400 mg etidronate disodium for 14 days followed by 500 mg elemental calcium for 76 days repeated in 3-monthly cycles) and 1 yr treatment-free follow-up. There was an overall increase in lumbar spine bone density (patients without fractures 2.6%, P < 0.001; with fractures 4.3%, P < 0.01) with minimal change at the femoral neck. The serum concentration of bone formation markers (osteocalcin and bone alkaline phosphatase) fell in response to treatment to a nadir at 6/12 (75 and 83% of baseline, respectively; P < 0.001). A cohort of patients (n = 29), 14 without fractures and 15 with fractures, was studied in more detail. After completion of treatment in the following treatment- free year, there was a resurgence of bone turnover (osteocalcin and bone alkaline phosphatase 117 and 122% of baseline, respectively; P < 0.05 and P < 0.01) with some evidence of maintenance of bone mass already gained. There is no evidence of persistent suppression of bone turnover after completion of treatment.      

Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice

Objectives—To compare the stability of brain natriuretic peptide (BNP) to that of N-terminal atrial natriuretic peptide (NT-ANP) in whole blood and plasma stored under different conditions. To compare a rapid, simple, direct (unextracted) BNP assay to a conventional assay using plasma extraction.
Design—Blinded, prospective, comparative study.
Setting—Tertiary referral cardiology department.
Subjects—Forty two subjects (24 men, 18 women) comprising 28 patients with left ventricular systolic dysfunction (LVSD) ranging from mild to severe and 14 healthy volunteers.
Main outcome measures—Stability of NT-ANP and BNP when stored as whole blood or plasma at room temperature over three days. Reproducibility of measurements.
Results—BNP was stable in whole blood stored at room temperature for three days; mean change in concentration −7.4% (95% CI 0.6 to −14.8), (direct), −6.3% (5.0 to −16.4), (extracted); whereas a significant decline in BNP concentration was noted in plasma stored at room temperature; −23.2% (−13.7 to −31.6), (direct); −14.4% (−3.2 to −24.3), (extracted). By contrast a small non-significant rise in NT-ANP concentration was noted both in whole blood and plasma stored at room temperature for three days; whole blood +8.6% (+22.3 to −3.5), plasma +6.3%, (23.2 to −8.4). The reproducibility of the BNP measurements, and particularly the rapid, direct, measurement, was superior to that for NT-ANP.
Conclusions—BNP is shown to be stable in whole blood for three days and can be measured using a rapid, simple assay. Routine assay of BNP is feasible in ordinary clinical practice and may be of value to general practitioners and hospital based physicians in the diagnosis and management of patients with LVSD. Samples can be sent to a central laboratory without special handling requirements.

Keywords: brain natriuretic peptide;  atrial natriuretic peptide;  heart failure;  diagnosis