Intra-articular clodronate in patients with knee osteoarthritis non-responder to intra-articular hyaluronic acid - a case report series of 9 patients with 8-month follow-up.

Background: Osteoarthritis (OA) is a common disease in the elderly people, inducing pain and functional limitations. Clodronate (CLO) a first generation non-nitrogen containing bisphosphonate has been purposed as a treatment of OA, being effective on pain, inflammation, bone marrow oedema, osteophytosis and cartilage regeneration. Intra-muscular routes of CLO showed efficacy in the treatment of Knee OA (KOA) and erosive OA of the hand. In KOA intraarticular CLO at low doses (0.5-2 mg) showed efficacy as well as hyaluronic acid (HA), being able to improve the effectiveness if associated to HA. Methods: Nine Consecutive patients (4 female, 5 male, mean age 78,22) with KOA at 2nd or 3rd degree following Kellgren-Lawrance scale, non responder to HA and unintended to surgery. They were treated with intraarticular CLO at the weekly dose of 20 mg, plus lidocaine 1% in 5 cc of saline solution for a route of 5 weekly infil-trations, followed by a second route of 5 intraarticular infiltrations 3 months after the first course. Visual analog score (VAS) pain and Tegner-Lysholm Score (TLS) were used to assess changes following CLO treatment. Results: Baseline pain was 6,77/10, reduced to 1,09 at day 150 (after second course) and to 2,3/10 at day 240. TLS at baseline was 56,7/100, improved to 96,7 at day 150 and to 84,1 at day 240. At day 240 only 2 out of 9 patients had a negative judgement of the treatment and decided to stop it, while 7 were satisfied and available to a further course. There was no increase of consumption of anti-inflammatory or analgesic drugs. A short time lasting pain after the injections was registered in all patients. Conclusions: In a small cohort of patients affected by KOA, non responders to intraarticular HA a higher dose of intraarticular CLO in KOA showed good compliance, amelioration of pain and functionality.

Use of clodronate in the management of osteoarthritis: an update.

Osteoarthritis (OA) is a chronic rheumatic disease characterized by joint cartilage wear and loss of normal function. Clodronate (CLO) is a first-generation non-nitrogen-containing bisphosphonate that exerts anti-inflammatory and analgesic and modulatory effects on bone and cartilage metabolism. To date, few clinical studies have evaluated the effect of CLO in OA. Current evidence suggests that CLO may represent a new type of analgesic drug as it reduces pain in bone diseases characterized by edema such as Complex Regional Pain Syndrone type-1 and vertebral fractures. Thanks to its anti-inflammatory and analgesic effects, CLO has been shown to afford benefit in knee OA, erosive OA of the hand, painful knee hip prosthesis and veterinary practice. Transforming growth factor ß1 has also been found to play an important role in the pathogenesis of OA. The present review article examines recent evidence on the potential use of CLO in the treatment of OA.

Multifocal osteonecrosis in a patient with anamnestic ulcerative colitis. Is there a relationship with the disease and the use of glucocorticoids twenty years before? A brief review of the literature.

In 2013 a 40 year old man came to visit in our Rheumatology Unit because of a recent bilateral shoulder and hip pain. He had been treated from 1990 to 2000 with Cyclosporin A and Sulfasalazyn because of an ulcerative colitis which was completely in remission from 2000 . Glucocorticoids at the mean daily dose of 50 mg were administered only in the first period (1990-92). X-plain rays showed a suspicious multifocal osteonecrosis of both femoral and humeral heads. Magnetic Resonance confirmed the diagnosis (stage III and IV following Ficat and Arlet's criteria). The patient was treated with a cycle of hyperbaric oxygen therapy, with two cycles of intravenous clodronate and with a 2-month cycle of teriparatide. The treatment was able to save a sufficient function for both shoulders, while for both hips arthroplasty the surgery was required. The risks of osteonecrosis linked to inflammatory bowel diseases or to its therapy are discussed.

CLODRONATE: OLD DRUG, NEW USES.

Clodronate (CLO) is a bisphosphonate (BP) with proved efficacy in the treatment of osteoporosis. The reason of its activity is the anti-resorptive action, which is a common characteristic of BPs. Contrary to other BPs, CLO has a relatively low affinity for bone and a peculiar mechanism of action. CLO is effective in several diseases associated to excessive bone resorption as bone Paget’s disease and CRPS type I. Moreover, there are data showing activity of CLO in the erosive osteoarthritis of the hands, in the osteoarthritis of the knees, in the treatment of extra-articular calcifications and in preventing the mobilization of knee and hip prosthesis.

Effects of monthly intramuscular neridronate in rheumatic patients in chronic treatment with low-dose glucocorticoids.

OBJECTIVES: To assess the effects of intramuscular (im) neridronate (NE) on lumbar and femoral neck BMD and on markers of bone turnover in rheumatic patients under chronic low-dose glucocorticoids (GC) therapy. METHODS: Sixty-nine osteopoenic and osteoporotic patients, affected by rheumatic diseases and gastric or esophageal conditions which contraindicated treatment with oral bisphosphonates (BPs), were randomly assigned to: Group A (23 patients) administered with daily calcium 1 g and vitamin D 800 UI; Group B (46 patients) receiving daily calcium 1 g, vitamin D 800 UI and im NE 25 mg monthly. RESULTS: After 12 months of therapy (M12) lumbar BMD was reduced of 2.97% in Group A, and improved of 3.34% (p=0.001) in Group B; at M12, femoral neck BMD was reduced of 2.40% in Group A and improved of 1.78% in Group B (p=0.010). After 6 (M6) and 12 months of therapy, the bone resorption markers were significantly reduced in Group B: OHPr-41.64% at M6 (p<0.001) and -37.91% at M12 (p<0.001); DPD-33.4% at M6 (p<0.001) and -33.18% (p<0.001) at M12: NTX -57.08% (p<0.001) at M6 and -55.95% (p<0.001) at M12; OC-11.62% (p=0.05) at M6 and -12.62% at M12 (p=0.06); B-ALP -13.95 % at M6 (p=0.04) and -0.85% at M12 (NS). CONCLUSION: A twelve-month intramuscular NE treatment in rheumatic patients under GCs therapy improves lumbar and femoral BMD and mainly reduces the markers of bone resorption.

Compared clinical efficacy and bone metabolic effects of low-dose deflazacort and methyl prednisolone in male inflammatory arthropathies: a 12-month open randomized pilot study.

OBJECTIVE: To evaluate: (i) a correct equivalence ratio of clinical efficacy between low-dose deflazacort (DFZ) and methyl prednisolone (MP); and (ii) bone metabolic effects of low-dose DFZ and MP in the treatment of male RA and PsA. METHODS: A total of 21 male patients with active RA or PsA, naive to steroid treatment were chosen for the study. Group I: 10 patients treated for 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD. Group II: 11 patients treated for 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD. At day 0, 90, 180, 240 and 360 evaluation of ACR improvement criteria; a blood sample for total and bone-specific ALP, calcium, phosphorus, PTH, SHBG, estradiol, ACTH, osteocalcin, LH, OPG; a sample of urine for calcium, phosphorus, creatinine and DPD. RESULTS: 13/21 patients (6/10 Group I; 7/11 Group II) reached ACR 20 at 6 months; 14/21 (7/10 Group I, 7/10 Group II) at 12 months. Only at the third month we observed in Group II vs Group I a reduction of OPG (24% vs 6%, P = n.s.); ALP (P < 0.001) and osteocalcin (P = 0.006) decreased in both groups from the third month; DPD decreased in both groups only from the sixth month (P = 0.002). CONCLUSIONS: The correct equivalence ratio of DFZ to MP is 1.875:1, and of DFZ to prednisolone 1.5:1. We found a relative prevalence of bone resorption compared to bone formation in the first 6 months of treatment. The trend of OPG requires further investigation.

[Phenobarbital rheumatism associated with gouty arthritis. Case report with 18-month follow-up]. / Associazione reumatismo gardenalico--artrite gottosa: caso clinico con follow-up di 18 mesi.

Anticonvulsivant-induced rheumatism has been described in the literature mostly in relation to phenobarbital therapy. We report the case of an 85-year-old male affected by generalized seizures and treated with phenobarbital for some months, who came to our observation on account of a long-lasting arthropathy which was diagnosed as unknown gouty arthritis. After treatment however, a clinical picture of shoulder-hand syndrome persisted: this latter disappeared after substitution of phenobarbital with phenytoin. The association of a syndrome of rheumatism induced by barbiturates with gouty arthritis has not been previously described in the literature.

Clarithromycin in rheumatoid arthritis patients not responsive to disease-modifying antirheumatic drugs: an open, uncontrolled pilot study.

OBJECTIVE: In 1996 we found by serendipity that 2 patients with rheumatoid arthritis (RA) who were taking clarithromycin (CM) to eradicate Helicobacter pylori experienced a regression of their RA symptoms. Following this observation, we tested the hypothesis that this reduction in symptoms could have been caused by CM administration. METHODS: We performed a 6-month, open, uncontrolled pilot study on 18 patients (14 females and 4 males, mean age 62 yrs.) with RA who had previously received DMARDs (mean 2.6) and discontinued the treatment at least one month earlier because lack of efficacy or severe side effects. Patients were treated with CM at the dose of 500 mg twice per day for the first 10 days, followed by a daily maintenance dose of 250 mg twice per day. RESULTS: 4/18 patients did not complete the treatment, 2/18 were not responsive to the treatment and 2/18 discontinued the treatment. Following ACR criteria the improvement was: 10 patients ACR 20; 6 patients ACR 50; and 2 patients ACR 70. The remaining 4 patients did not reach ACR 20 since either the number of tender or swollen joints was not to the level required. Reductions in PGE2 and soluble phospholipase A2 plasma levels were closely related to CM plasma levels. CONCLUSIONS: Ourfindings suggest that CM treatment can be beneficial in those patients who are not responsive to or cannot tolerate DMARDs. No definitive conclusions can be drawn based on the present study, due to the small sample size involved.