Kwok n Ma

Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: A 12-month randomized controlled trial

OBJECTIVES To evaluate the effect of switching from oral bisphosphonates to denosumab on bone mineral density (BMD) in long-term glucocorticoid users. METHODS Adult patients who were receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) and oral bisphosphonates (≥2 years) were recruited. Participants were randomized to either continue oral bisphosphonates or switch to denosumab (60 mg subcutaneously every 6 months) for 12 months. Serial BMD (lumbar spine, hip) and bone turnover markers (serum osteocalcin, P1NP, β-CTX) were measured. RESULTS 42 women were recruited (age 54.7±12.9 years; 21 shifted to denosumab and 21 continued on bisphosphonates). The duration of prednisolone therapy was 101±66.3 months and the daily dose was 4.4±2.1 mg. Baseline demographic data, osteoporosis risk factors, and BMD at various sites were similar between the two groups of patients. At month 12, BMD of the spine and hip increased by +3.4±0.9% (p=0.002) and +1.4±0.6% (p=0.03), respectively, in the denosumab group; whereas the corresponding change was +1.5±0.4% (p=0.001) and +0.80±0.5% (p=0.12) in the bisphosphonate group. The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD and β-CTX values, and other confounding factors (p=0.01). Bone turnover markers (β-CTX and P1NP) were more strongly suppressed by denosumab than the bisphosphonates. Minor infections were more common in denosumab-treated patients while other adverse events occurred at similar frequencies between the two groups. CONCLUSIONS In patients receiving long-term glucocorticoids, switching from oral bisphosphonates to denosumab resulted in greater gain of the spinal BMD and suppression of bone turnover markers after 12 months of therapy. The results have to be confirmed by a larger clinical trial with fracture as endpoint.

Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial

Objectives To study the efficacy of raloxifene in preventing bone mineral density (BMD) loss in women receiving long-term glucocorticoids (GC). The study took the form of a parallel-group randomised double-blinded placebo-controlled trial. Methods Postmenopausal women without hypercoagulability risk factors who were prevalent GC users were randomised to receive either raloxifene (60 mg/day) or placebo (1 tablet/day) on top of calcium (1000 mg/day) and calcitriol (0.25 μg/day). BMD of the hip and spine (primary outcome), bone turnover markers and new vertebral fractures (secondary outcomes) at month 12 were assessed. Results Between December 2006 and December 2008, 114 patients were recruited (age 55.3±7.7 years). The duration and dose of prednisolone received was 62.2±64 months and 6.7±5.9 mg/day, respectively. Baseline vertebral fracture was present in six (5%) patients. In all, 57 patients were allocated to each of the treatment arms. Demographic data, osteoporotic risk factors and BMD at various sites were similar between the two groups of patients. At month 12, a significant gain in the lumbar spine (+1.3±0.4%; p=0.004) and total hip BMD (+1.0±0.4%; p=0.01) was observed in patients treated with raloxifene but a significant decrease in BMD of the lumbar spine (−0.9±0.4%; p=0.045) and hip (−0.8±0.3%; p=0.01) occurred in the placebo group. The femoral neck BMD did not change significantly in favour of raloxifene. Three new fractures developed exclusively in the patients treated with placebo. Bone formation (serum osteocalcin and procollagen type I N-terminal) and resorption (urine deoxypyridinoline and type I collagen) markers decreased significantly in the raloxifene group but not in patients treated with placebo. Leg cramps were numerically more frequent in the raloxifene group (7% vs 0%) but thromboembolism was not reported in any patients. Conclusions In postmenopausal women receiving long-term GCs, raloxifene is well tolerated and significantly increases spinal and hip BMD after 12 months of treatment.

Bone mineral density and body composition in men with systemic lupus erythematosus: a case control study.

OBJECTIVE To study the bone mineral density (BMD) and body composition in men with systemic lupus erythematosus (SLE). METHODS Consecutive male patients who fulfilled > or =4 ACR criteria for SLE and age-matched healthy men were recruited for measurement of BMD and body composition by DXA scan. Risk factors for low BMD in SLE patients were evaluated. RESULTS 40 male SLE patients were studied (age 42.6+/-12 years; disease duration 84.7+/-79 months). 34 (85%) patients were treated with long-term glucocorticoids. Compared with 40 controls, SLE patients had a significantly lower BMD at the lumbar spine (0.96+/-0.16 vs 1.03+/-0.11 g/cm2; p=0.02) and the hip (0.87+/-0.14 vs 0.94+/-0.12 g/cm2; p=0.04). At the spine, 12 (30%) SLE patients had Z scores< - 2.0 and 2 (5%) had osteoporotic fractures. At the hip, 3 (7.5%) patients had Z scores< - 2.0 but none had hip fractures. The BMD Z scores at the femoral neck and spine were significantly lower in SLE patients than controls. The total lean body mass was also lower in patients than control subjects (46.4+/-7.3 vs 50.5+/-5.9 kg; p=0.01). Multiple regression revealed increasing age, habitual drinking, lower BMI and use of high-dose prednisolone were unfavorably associated with lower BMD at the spine in SLE patients. CONCLUSIONS Reduced BMD and lean body mass are prevalent in men with SLE. Appropriate measures against osteoporosis should be undertaken, especially in older patients with low BMI who receive high-dose glucocorticoids.

Prevalence and risk factors of low bone mineral density in Chinese patients with systemic sclerosis: a case–control study

OBJECTIVE To study the prevalence and risk factors of low BMD in patients with SSc. METHODS Consecutive patients with SSc and an equal number of age- and gender-matched healthy subjects were screened for BMD, fat and lean mass by DXA scan. BMD, body composition and osteoporosis risk factors were compared between patients and controls. Associated factors for low BMD in SSc patients were studied by linear regression. RESULTS A total of 84 patients with SSc were studied [89% women; age 49.4 (11.3) years; 21% diffuse subtype; disease duration 7.8 (6.4) years]. Except for significantly lower BMI (P = 0.001), fat mass (P = 0.02) and lean body mass (P = 0.006) observed in SSc patients, the prevalence of other osteoporosis risk factors was similar to controls. Fourteen (17%) and five (6%) SSc patients had low BMD expected for age (z-score <-2.0) at the lumbar spine and hip, respectively. BMD of the lumbar spine, hip, femoral neck and whole body was significantly lower in SSc patients than controls, adjusted for age, sex, menopause and BMI (P < 0.05 in all; effect size 0.44-0.54). Linear regression revealed increasing age, menopause and low BMI were independently associated with low BMD at the spine or hip in SSc patients. However, BMD did not correlate with the severity of involvement of the skin and other systems. CONCLUSION BMD of the spine and hip is significantly lower in patients with SSc than in healthy subjects, which is independent of age, sex, menopause, low BMI and altered body composition.

Childhood-onset disease carries a higher risk of low bone mineral density in an adult population of systemic lupus erythematosus

OBJECTIVE To study the BMD of patients with SLE according to the age of disease onset. METHODS Consecutive SLE patients were screened for BMD at the hip, lumbar spine and whole body by the dual-energy X-ray absorptiometry (DXA). Comparison was made between patients who had disease onset in childhood (<18 years) and adulthood (≥18 years). Factors associated with low BMD were studied by linear regression. RESULTS A total of 395 SLE patients were studied (94% women; 11% childhood-onset disease). Osteoporosis of the lumbar spine and the hip/femoral neck was present in 20 and 10% of the patients, respectively. Childhood-onset SLE patients were less likely to be post-menopausal, but had significantly lower BMI, longer SLE duration and a higher frequency of ever use of high-dose CSs, CYC and AZA. Despite a significantly younger age, the BMD of the hip, femoral neck and lumbar spine was significantly lower in childhood- than adult-onset SLE patients. In linear regression models, childhood-onset disease was an independent factor for lower BMD at the lumbar spine (β = -0.18; P = 0.002), hip (β = -0.20; P = 0.001) and femoral neck (β = -0.16; P = 0.01) after adjustment for age, sex, BMI, smoking, menopause, SLE duration and damage index, duration and current dose of prednisolone treatment and the ever use of high-dose glucocorticoids, other immunosuppressive agents, calcium, vitamin D and the bisphosphonates. CONCLUSIONS In adult SLE patients, childhood-onset disease carries a higher risk of osteoporosis, which may possibly be related to a higher cumulative dose of glucocorticoids used for more active disease and failure to achieve a normal peak bone mass during puberty.

Protein-losing enteropathy associated with or without systemic autoimmune disease: what are the differences?

Objective The aim of our study was to compare protein-losing enteropathy (PLE) associated with or without systemic autoimmune (SA) diseases. Methods Patients diagnosed with PLE were selected, and their clinical characteristics, laboratory, endoscopic and imaging characteristics, treatment, and outcome were analyzed. Results From 2001 to 2010, 74 patients (60 patients with SA disease) with a female predominance were diagnosed with PLE. The SA group tended to be younger, presented early (4.3 vs. 7 weeks, P=0.08), and had significantly more mucocutaneous–articular involvement (16.7 vs. 0%, P<0.05; 50 vs. 0%, P<0.02; 43.3 vs. 0%, P<0.01), compared with the other group, which showed more weight loss (64.3 vs. 25%, P<0.01), malaise and fatigue (57.1 vs. 28.3%, P<0.02), and tended to have more gastrointestinal (GI) symptoms. The SA group was associated with lymphopenia (0.8 vs. 2.7×109/l, P<0.01), hyperglobulinemia (43 vs. 31.2 IU/l, P<0.04), lactate dehydrogenase (511.1 vs. 393.5 IU/l, P<0.05), hematuria (48.3 vs. 7.1%, P<0.01), and pyuria (23.3 vs. 0%, P<0.03), whereas the non-SA group had a higher platelet count (402 vs. 262.5×109/l, P<0.01) and alkaline phosphatase (111 vs. 78.2 IU/l, P<0.03) on admission. A subgroup analysis of patients with SA disease showed that more lupus patients had pericardial effusion (14.6 vs. 0%, P=0.08), polyarthritis (50 vs. 16.7%, P=0.02), lower C3 level (0.5 vs. 0.85 mg/l, P<0.01), antinuclear factors (89.6 vs. 58.3%, P<0.01), and antiextractable nuclear antigen antibody (73.3 vs. 37.5%, P<0.03), whereas nonlupus patients had higher C-reactive protein (87.9 vs. 40 mg/l, P<0.01) and more antineutrophil cytoplasmic antibody (ANCA) (60 vs. 3%, P=0.00). Thirty-seven (71%) patients with SA disease had diffuse nonerosive erythematous GI mucosa with chronic inflammatory cells in the lamina propria layer, and 12 (85.7%) patients without SA disease had focal lesions. The treatment response was comparable between the two groups. However, the time required to normalize the serum albumin level (6.3 vs. 12.3 months, P=0.02) of patients with SA disease was much shorter than that of the non-SA group and those of inflammatory markers, specifically, C-reactive protein and complement C3, of its own group (6.3 vs. 11.6 vs. 12.1 months, P<0.04). More patients without SA disease had infective episodes during the management period (14.3 vs. 1.7%, P<0.01). Conclusion Patients with PLE associated with SA disease tend to have a distinct clinical syndrome with regard to the extent of clinical manifestations and laboratory, endoscopic, and histological features compared with those without. Patients without SA disease are more prone to develop complications and mortality. However, both can be effectively treated with comparable treatment response.

THU0242 Incidence and risk factors for low bone mineral density in patients with systemic sclerosis (SSC): A case-control study

Objectives To study the bone mineral density (BMD) and body composition (BC) in Chinese patients with systemic sclerosis (SSc), and the risk factors for low BMD. Methods Consecutive patients who fulfilled the ACR criteria for SSc were screened for BMD and BC (fat and lean mass) by dual energy X-ray absorptiometry (DXA) scan (Hologic, Belford USA). Exclusion criteria were: (1) Age <18 years; (2) Informed consent could not be obtained. An equal number of age and gender matched healthy controls were also recruited for the same measurements. The extent of skin involvement was assessed by the modified Rodnan skin score (mRSS) and organ damage was evaluated by the Medsger SSc severity index. Risk factors for low BMD were studied by linear regression analyses. Results 77 patients with SSc and 77 controls were studied (91% women). The mean age of SSc patients was 42.7±14 years and the mean disease duration was 7.8±6.6 years. Sixteen (21%) patients had diffuse SSc while the others had limited SSc. Only 5 (6%) patients were receiving bisphosphonates. According to the WHO criteria, 9 (12%) patients with SSc had osteoporosis (T score ≤-2.5) at the hip and 26 (34%) patients had osteoporosis at the lumbar spine. The incidence of osteoporosis at the hip and lumbar spine was significantly higher than that in normal controls (hip 1%; p=0.008, lumbar spine 14%; p=0.004). Osteopenia of the hip and spine (T score between -1 and -2.5), occurred in 58% and 36%, respectively, of the SSc patients. Four (5%) patients had personal history of fractures, all of which were non-vertebral fractures. The body weight (BW) of patients with SSc was significantly lower than controls (52.5±9.9 vs 56.4±8.3kg; p<0.001). After adjustment for age, body mass index (BMI) and other osteoporosis risk factors, BMD of the total hip (0.786±0.138 vs 0.857±0.118g/m2; p=0.01) and femoral neck (0.674±0.123 vs 0.734±0.117g/m2; p<0.001) were significantly lower in patients with SSc than controls. The BMD of the lumbar spine (L2-4) was also significantly lower in SSc patients (0.894±0.155 vs 0.972±0.148g/m2; p=0.001). On the other hand, the total bone mineral content (BMC) (1.76±0.34 vs 1.92±0.30g; p=0.002) and lean body mass (32.9±5.3 vs 35.1±5.6kg; p=0.01) were significantly lower in patients with SSc than controls. The median mRSS score and total Medsger severity index of the SSc patients was 8 (IQR 4-13) and 3 (IQR 1-6), respectively. Logistic regression analysis revealed a significant correlation between mRSS score and BMD of the total hip (OR 1.12[1.004-1.24] per point; p=0.04) but not with the lumbar spine (OR 1.10[0.996-1.210] per point; p=0.06) after adjustment for age, sex and BMI. The total Medsger severity score correlated positively but insignificantly with osteoporosis of the lumbar spine (OR 1.01[0.87-1.17]; p=0.90) or the hip (OR 1.15[0.98-1.35]; p=0.09). Increasing age was the other independent and adverse factor related to both osteoporosis of the hip and spine (p<0.01 in both). Conclusions Patients with SSc have significantly lower BMD at lumbar spine, hip and femoral neck, as well as lean body mass than age and gender matched healthy controls. Osteoporosis of the hip correlates significantly with the extent of skin involvement but not with organ damage. Disclosure of Interest None Declared