Use of clodronate for painful knee prosthesis in osteoarthritis patients: a 6-month pilot study.

BACKGROUND: Knee replacement surgery is one of the most common surgical procedures performed worldwide. Unfortunately, knee prostheses can become painful over time, necessitating appropriate analgesic treatment. Bisphosphonates such as clodronate (CLO) may play an important role in the treatment of painful knee prostheses by virtue of its analgesic and anti-inflammatory properties. METHODS: In this prospective open label pilot study, eighteen consecutive patients aged 73.2±8.9 years affected by knee painful prosthesis and osteoarthritis were treated with a rehabilitation cycle in addition to i.v. or i.m. CLO. Induction dose was 2.0-2.1g, followed by a weekly dose of 200 mg (i.m.) for 6 months. Visual analogue scale (VAS) pain score and Tegner Lysholm Score (TLS) were used to assess improvement following CLO treatment. RESULTS: Thirteen out of 18 patients completed the 6-month follow-up. VAS pain score decreased from 8.1±1.8 at baseline to 5.6±2.6 (P<0.05) and TLS increased from 40.4±20.3 at baseline to 62.7±24.1 at 6 months (P<0.05). Univariate regression revealed that among a range of variables, BMI was positively correlated with VAS (r=0.73, P=0.004) and lower TLS after 1 month (r= -0.62, P=0.006). CONCLUSIONS: CLO in association with rehabilitation exercises can reduce pain and ameliorate the functionality of painful knee prostheses. Administration of a high dose (induction dose) of CLO every 3 months appears to be the most effective regimen compared to a weekly maintenance dose.

Permanent Discontinuation of Glucocorticoids in Polymyalgia Rheumatica Is Uncommon but May Be Enhanced by Amino Bisphosphonates.

OBJECTIVE: The duration of treatment with glucocorticoids (GC) in polymyalgia rheumatica (PMR) is often longterm. Amino bisphosphonates (N-BP) are used in PMR for the prevention of GC-induced osteoporosis, but they coulsd also have immunomodulatory properties. Whether they can be effective as an adjuvant treatment in PMR is unknown. We aimed to establish whether the use of N-BP in our PMR cohort may be associated with GC discontinuation. METHODS: We conducted a retrospective review of all patients diagnosed with PMR recorded in our electronic medical notes. Cox regression analyses were used to examine the association between the use of N-BP and discontinuation of GC. RESULTS: Data were retrieved for 385 patients (mean age 71 ± 10 yrs, 64% females, mean initial prednisone dose 19 ± 9 mg/day). The median followup time was 38 months (range 9-57); more than 60% of patients were exposed to N-BP. GC were discontinued in 47% of patients after a median time of 20 months (range 14-27), but subsequently restarted in 39%. Overall, 276/385 patients (72%) were actively treated at their last available evaluation (mean prednisone dose 4.9 ± 5.5 mg/day), while 123/205 (60%) were still receiving GC after 24 months of followup. The use of N-BP was associated with the discontinuation of GC (adjusted HR 0.66, 95% CI 0.50-0.88), independent of age, initial GC dose, and osteoporosis. CONCLUSION: Unlike current guidelines, longterm treatment with GC is often necessary. These preliminary data suggest that N-BP may be involved in the management of PMR.

Parathyroid hormone is a determinant of serum Dickkopf-1 levels in ankylosing spondylitis.

Available studies reported contradictory results about serum levels Dickkopf-1 (DKK1), an inhibitor of Wnt signaling in patients with ankylosing spondylitis (AS). In previous studies, we observed in other conditions that parathyroid hormone (PTH) serum levels were an important determinant of DKK1 serum levels. The aim of the present study was to investigate it in patients with AS. We recruited 71 patients diagnosed with AS. Levels of C-reactive protein (CRP), DKK1, PTH, 25OH-vitamin D, and bone turnover markers (intact N-propeptide of type I collagen, P1NP, and C-terminal telopeptide of type I collagen, CTX) were measured and compared to healthy controls (HC). Dual X-ray absorptiometry at lumbar spine and proximal femoral site was used for bone mineral density (BMD) assessment and spine X-rays were also performed. PTH serum levels were found to be significantly higher in AS patients than in HC (33.8 ± 14.11 vs 24.8 ± 13 pg/ml, p = 0.002), while mean DKK1 serum levels were lower than in HC (23.3 ± 13.1 vs 29.8 ± 15.9 pmol/l, p = 0.009). A positive correlation between DKK1 and PTH (correlation coefficient + 0.25, p = 0.03) was observed; it remained significant in a multivariate analysis. In patients with longer disease duration, DKK1 was also positively correlated with CTX (coefficient 0.42, p = 0.01), and PTH was higher in those patients with low BMD (Z-score ≤ - 1) at any site (p = 0.04). Also in AS, PTH is an important determinant of DKK1 serum levels and should be evaluated in studies on DKK1. PTH might have a role in bone involvement in AS, also through the Wnt pathway.

Higher Level of Dickkopf-1 is Associated with Low Bone Mineral Density and Higher Prevalence of Vertebral Fractures in Patients with Ankylosing Spondylitis.

Patients with ankylosing spondylitis (AS) have an increased risk of bone loss and vertebral fractures. In this study, we explored the hypothesis that the excess bone loss and vertebral fractures might be related with the activity of the Wingless signaling pathway, and in particular with the serum levels of its circulating inhibitors, Sclerostin and Dickkopf-1 (DKK1). We recruited 71 patients diagnosed with AS. Lateral radiographs of the total spine were analyzed to detect the presence of vertebral fractures, and bone mineral density (BMD) was assessed in all patients using dual X-ray absorptiometry at lumbar spine and proximal femoral site. Blood samples were obtained and levels of C-reactive protein (CRP), DKK1, and Sclerostin were measured. Blood samples from 71 healthy sex- and age-matched volunteers were collected to be used as controls. Vertebral fractures were detected more commonly among men than in women (29 vs 8 %, respectively). DKK1, but not Sclerostin serum levels, were inversely correlated to lumbar spine Z-score BMD. Patients with one or more prevalent vertebral fractures had significantly higher DKK1 levels, without significant difference in Sclerostin serum levels. A significant positive correlation was found between DKK1 serum levels and CRP (r = 0.240, p = 0.043). The association we found between serum DKK1 levels and BMD values and vertebral fracture prevalence suggests that DKK1 might contribute to the severity of osteoporosis in AS.