The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture

Abstract

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, no study has so far evaluated the effects of anti-osteoporotic therapy on BMD in haemophilia.The primary endpoint of this prospective study was to estimate the effect of 12-month therapy of oral ibandronate 150 mg/month on BMD in patients with haemophilia A and B. Secondary endpoint was its effect on turnover markers (BTM) of bone resorption [serum C-terminal telopeptide of type 1 collagen (sCTX), tartrate-resistant acid phosphatase band 5b] and bone formation (osteocalcin and bone-specific alkaline phosphatase. Ten adult patients with T-score < -2.5 SD or Z-score < -2 and/or increased risk of fracture according to FRAX model were included. All received 1,000 mg/day calcium carbonate with 800 IU/d cholecalciferol. Males with haemophilia A (n=7) or B (n=3) (mean age 43.5 ± 13.5 years) were studied. Ibandronate resulted in an increase in lumbar BMD (from 0.886 ± 0.169 to 0.927 ± 0.176 g/cm2, 4.7%, p=0.004). No change in BMD of total hip (from 0.717 ± 0.128 to 0.729 ± 0.153 g/cm2, p=0.963) or femoral neck (0.741 ± 0.135 to 0.761 ± 0.146 g/cm2, p=0.952) was noticed. Ibandronate led to a decrease in sCTX (from 0.520 ± 0.243 to 0.347 ± 0.230 ng/ml, -29.9%, p=0.042). No change was observed in other BTM. Ibandronate was generally well-tolerated. In conclusion, ibandronate significantly improved BMD in lumbar spine and reduced bone resorption in adults with haemophilia at increased risk of fracture. Its effect on hip BMD and bone formation markers was not significant.

Predictors of Ibandronate Efficacy for the Management of Osteoporosis: A Meta-Regression Analysis

“…Thirty four studies [ 14 – 58 ] including 28 randomized controlled, 1 non-randomized controlled [ 15 ], 4 prospective observational [ 26 , 30 , 36 , 57 ], and 1 retrospective [ 50 ] studies fulfilled eligibility criteria. A flowchart of study screening and selection process is presented in Fig 1 .…”

Dose-Effectiveness Relationships Determining the Efficacy of Ibandronate for Management of Osteoporosis

“…Results of these trials were published in 45 articles 10 – 54 and a flowchart summarizing study screening and the selection process is presented in Figure 1 . Briefly, the following studies were included in the meta-analysis: 28 randomized controlled, 1 nonrandomized controlled, 11 4 prospective observational, 22 , 26 , 32 , 53 and 1 retrospective 46 study. Of the studies included, their important characteristics are presented in Table S1, http://links.lww.com/MD/A306 .…”

Osteoporosis Remains Constant in Patients with Hemophilia—Long-Term Course in Consideration of Comorbidities

“…17 Anagnostis et al examined the effect of bisphosphonates in PWH, detecting a reduction of bone resorption along with a BMD enhancement on lumbar spine. 18 One-third of our patients were repetitively treated with oral or local glucocorticoids on demand during the observation period. But although glucocorticoids are a known risk factor for osteoporosis due to inhibition of the body's vitamin D production and osteoblasts' activity, 19 no significant decline in t-score could be identified compared with the participants not receiving glucocorticoids.…”