Bone-sparing effects of tocilizumab in rheumatoid arthritis: a monocentric observational study.

Introduction: Bone loss is a common feature in several autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis (RA). Indeed, the high levels of pro-inflammatory cytokines seem to enhance bone resorption and to diminish bone formation, thus producing an uncoupling between osteoclast and osteoblast function and favoring the onset of juxtarticular as well as systemic osteoporosis. Many papers underline the high prevalence of osteoporosis in RA, as well as the negative correlation between interleukin 6 (IL-6) serum levels and bone mineral density (BMD). The aim of this study was to assess the effectiveness of one-year treatment with tocilizumab (TCZ), the first approved IL-6 receptor inhibitor, in reducing bone loss in RA. Material and methods: We enrolled 18 patients fulfilling 2010 ACR and EULAR criteria for RA from our arthritis outpatient clinic, assessing clinical and biochemical parameters during a 12-month period. The patients received TCZ 8 mg/kg i.v. every 4 weeks and underwent dual energy X-ray absorptiometry (DXA) for the measurement of bone mineral density (BMD) at baseline and at the end of study. Serum levels of C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), IL-6, serum CrossLaps, osteoprotegerin (OPG), receptor activator of nuclear factor κß ligand (RANK-L) and dickkopf-1 (DKK-1) were measured at baseline, at 6 months and 1 year. Results: No significant difference in IL-6, RANK-L, DKK-1, OPG and serum CrossLaps levels between baseline, 6 months and 1 year were found. A significant increase of lumbar spine BMD was evidenced after 1 year of TCZ treatment. No difference in total body and femoral neck BMD was documented the end of the study. Conclusions: This study suggest the bone-sparing effect of TCZ in RA affected individuals.

Efficacy of intravenous neridronate in transient osteoporosis of the hip.

OBJECTIVES: To evaluate the efficacy and safety of intravenous (iv) neridronate in patients affected by transient osteoporosis of the hip (TOH). METHODS: We retrospectively evaluated the clinical records of patients affected by TOH treated with iv neridronate in our department. We treated patients with a value of visual analogue scale (VAS)-pain ≥ 80/100 mm at diagnosis, limited range of movement and magnetic resonance images (MRI) findings suggestive of TOH. The regimen used was: one iv infusion at day 0, 3, 6, 9 (100 mg for each infusion: total of 400 mg). This protocol was repeated in refractory cases. Recovery was defined as VAS-pain level ≤20/100. Concomitant use of analgesics was allowed. Paired Student t-test was used to assess VAS-pain change. RESULTS: Five patients were male, 3 were female. Mean age was 54.5±2.12 years old. Mean body mass index was 26.57±2.22. Mean time to diagnosis, since the onset of the symptoms, was 75±21.21 days. Mean number of neridronate infusions was 7.5±2.56. Mean time of recovery was 57±45.96 days. Mean VAS-pain at baseline was 84±2,24. Mean VAS-pain after treatment was significantly reduced (p<0.001) with a value of 12.12±6.46. None of the patients needed analgesics after treatment. No adverse event was reported. In 5 cases, post-treatment MRI showed complete bone marrow oedema resolution. CONCLUSIONS: Intravenous neridronate is effective and safe in the treatment of TOH and its use may lead to a faster resolution of the disease.

Intramuscular Clodronate in Long-Term Treatment of Symptomatic Knee Osteoarthritis: A Randomized Controlled Study.

BACKGROUND AND OBJECTIVE: Clodronate is a nitrogen-free bisphosphonate that is widely and effectively used in the treatment of many osteo-metabolic disorders. The objective of our study was to evaluate the effectiveness of clodronate in reducing pain and bone marrow edema in knee osteoarthritis. METHODS: In total, 74 patients were included in the study. Group 1 received intramuscular clodronate 200 mg daily for 15 days and then once weekly for the next 11.5 months; group 2 received intramuscular clodronate 200 mg daily for 15 days and then once weekly for the next 2.5 months. Visual analog scale (VAS) scores were recorded at baseline (T0) and after 30 days (T1), 3 months (T2), 6 months (T3), 9 months (T4), and 12 months (end of study; T5). We also evaluated functional status and use of paracetamol (T0, T1, T2, T3, T4, and T5) and changes in Whole Organ Magnetic Resonance Imaging Score (WORMS; T0, T2, and T5). RESULTS: Both groups had a statistically significant reduction in VAS score until 3 months. Group 1 then experienced further VAS reductions, whereas VAS scores for group 2 progressively increased. Pain, stiffness, and physical function also showed the same trend, as did bone marrow edema extension, which was evaluated with WORMS. CONCLUSION: Our study indicates that intramuscular administration of a therapeutic dose of clodronate followed by a maintenance dose is effective in the management of symptomatic knee osteoarthritis, improving functional outcomes and reducing pain and bone marrow edema. Prolonged treatment increases the long-term efficacy of clodronate compared with the shorter schedule.

Improved efficacy of intramuscular weekly administration of clodronate 200 mg (100 mg twice weekly) compared with 100 mg (once weekly) for increasing bone mineral density in postmenopausal osteoporosis.

BACKGROUND: Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved. OBJECTIVE: The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported. METHODS: The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57-78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years. RESULTS: Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (± SD) at the lumbar spine of +4.0 % (± 2.1) and +5.9 % (± 2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (± 1.7) and +3.5 % (± 2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (± 1.7) and +5.4 % (± 1.8) at 1 and 2 year(s), respectively, compared with a change of +2.3 % (± 1.9) and +2.5 % (± 1.9), respectively, registered in Group A. Consistently, the BMD increase measured at the total femur was significantly higher for Group B [+3.4 % (± 1.9) and +4.9 % (± 2.1) at years 1 and 2, respectively] compared with Group A [+1.6 % (± 0.9) and +2.4 % (± 1.9) at years 1 and 2, respectively]. When the change in BMD from year 1 to year 2 was compared, a significant increase of BMD was seen in Group B in all the analysed regions, contrary to that observed for Group A where a plateau effect resulted in no significant change from year 1 to year 2. Three non-traumatic vertebral fractures occurred during the study: two in Group A and one in Group B. CONCLUSION: The present study indicates the superior performance of IM clodronate 200 mg weekly (100 mg twice weekly) compared with 100 mg once weekly in BMD in women with postmenopausal osteoporosis. This work demonstrated that administration of twice the drug dosage in a week significantly improved the efficacy of the treatment without inducing serious adverse events. Therefore, IM clodronate 200 mg weekly may be considered a valid therapeutic choice for the treatment of postmenopausal osteoporosis.