AB030. Study of bone turnover markers and treatment monitoring in osteogenesis imperfecta

Bisphosphonates (BPs) are widely used for treatment of osteogenesis imperfecta (OI). However, prolonged use may be associated with suppression of bone turnover, the exact molecular mechanism of which is poorly understood. The objective of this study was to evaluate the effect of zoledronic acid (ZOL) on precursor osteoclasts by studying caspase 3 activity. A total of 15 children participated in the study (n = 10 OI patients, n= 5 controls). Out of the 10 OI children, 5 had received a cumulative dose of <30 mg and 5 received > 30 mg of ZOL. Isolated mononuclear cells were studied for caspase 3 activity from all study participants. The mean age of study participants was 7 ±1.5 years. Six of them had OI type IV, two had type III and one had types I & II each. Radiographs showed “zebra stripe sign” and dense metaphyses; suggestive of acquired osteosclerosis. Bone turnover markers (PINP and CTx) were suppressed in all OI patients compared to controls. Caspase-3 activity was significantly increased in precursor osteoclasts cells at higher doses of BPs (>30 mg). Overzealous use of ZOL in OI suppresses bone turnover markers (P1NP, CTx) causes osteosclerosis and increased expression of caspase 3 activity in precursor osteoclasts which results in adynamic bone.

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Bone turnover markers in patients with osteogenesis imperfecta

Bone ◽

10.1016/j.bone.2004.02.023 ◽

2004 ◽

Vol 34 (6) ◽

pp. 1013-1016 ◽

Cited By ~ 44

Author(s):

Vania Braga ◽

Davide Gatti ◽

Maurizio Rossini ◽

Francesca Colapietro ◽

Elia Battaglia ◽

...

Keyword(s):

Bone Turnover ◽

Osteogenesis Imperfecta ◽

Bone Turnover Markers ◽

Turnover Markers

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Monthly intravenous alendronate treatment can maintain bone strength in osteogenesis imperfecta patients following cyclical pamidronate treatment

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0071 ◽

2020 ◽

Vol 33 (11) ◽

pp. 1391-1397

Author(s):

Daisuke Harada ◽

Hiroko Kashiwagi ◽

Kaoru Ueyama ◽

Kyoko Oriyama ◽

Yuki Hanioka ◽

...

Keyword(s):

Bone Turnover ◽

Osteogenesis Imperfecta ◽

Bone Strength ◽

Bone Turnover Markers ◽

Bone Fragility ◽

Mineral Density ◽

Before And After ◽

Alendronate Treatment ◽

Z Scores ◽

Turnover Markers

AbstractObjectivesOsteogenesis imperfecta (OI) is a skeletal dysplasia characterized by recurrent fractures due to congenital bone fragility. The only bisphosphonate approved for OI in Japan is pamidronate (PAM). To investigate whether monthly intravenous alendronate (ALN) infusions can maintain bone strength in OI children following cyclical PAM treatment.MethodsA prospective and non-inferiority study was conducted. Eight school-age OI patients aged 8.5±2.0 years who were treated with cyclical PAM for 6.0±2.3 years were enrolled and switched to monthly intravenous ALN (0.030 mg/kg/month). Changes in L1-4 bone mineral density (BMD) Z-scores, fracture rates, and bone turnover markers for 12 months were analyzed.ResultsAverage BMD Z-scores were −3.0±1.9, −2.9±2.0, and −2.2±2.0 in 12 months before enrollment, at enrollment, and after 12 months of ALN treatment, respectively. BMD Z-scores increased significantly during treatment with both PAM and ALN (p=0.012), and the effect of ALN was not inferior to that of PAM (p=0.67). There was no change in fracture rates (p=0.86) and bone turnover markers during the 12 months before and after enrollment. Additionally, ALN showed no remarkable side effects.ConclusionsOur results suggest that monthly intravenous ALN can maintain bone strength after primary usage of cyclical PAM. We concluded that monthly intravenous ALN as a maintenance treatment following cyclical PAM administration can be an option for OI children.

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The influence of ibandronate treatment on bone density and biochemical bone markers in patients with osteogenesis imperfecta

Orthopedic Reviews ◽

10.4081/or.2012.e29 ◽

2012 ◽

Vol 4 (3) ◽

pp. 29 ◽

Cited By ~ 4

Author(s):

Ingmar Ipach ◽

Torsten Kluba ◽

Petra Wolf ◽

Bertram Pontz ◽

Falk Mittag

Keyword(s):

Alkaline Phosphatase ◽

Bone Density ◽

Bone Turnover ◽

Osteogenesis Imperfecta ◽

Bone Turnover Markers ◽

Total Serum ◽

Type I ◽

Urinary Creatinine ◽

Urine Creatinine ◽

Turnover Markers

Osteogenesis imperfecta (OI) is characterized by different signs including increased bone fragility, short stature, blue sclera, abnormal tooth growth and often secondary immobility. No curative therapy has been found for this rare disease up to now, and different pharmacological substances have been tried as treatment for severe forms of OI. Promising results were seen with intravenous bisphosphonates in the treatment of patients with OI. The aim of present study was to show the effect of intravenous ibandronate therapy on bone density and bone metabolism markers. We analyzed the data of 27 patients with the diagnosis of OI who were treated off-label with intravenous ibandronate. Ibandronate was administered by intravenous infusion every three months at a dosage of 0.3-2 mg. Bone turnover markers and bone density were measured before starting therapy and every three months during treatment. Bone density was measured by using an ultrasound imaging system providing an accurate image of the calcaneus and by evaluating broadband ultrasound attenuation (BUA). Twenty-seven patients were treated with intravenous iban- dronate during the observation period. 18 were female. The mean age of all patients was 23.9 years ± 19.6 (range 4-63). Seventeen patients were categorized to have OI Type I, 5 patients to have OI Type III and 5 patients to have OI Type IV. There was a statistically significant decrease in total alkaline phosphatase (P<0.0001). We detected also a statistically significant decrease in the ratio urinary deoxypyridinoline/urinary creatinine (P=0.0048) and the ratio urinary pyridinoline/urinary creatinine (P<0.0001) respectively. There was also a statistically significant increase in serum magnesium (P=0.034) and BUA (P=0.0071). No statistically significant changes were seen for total serum calcium (P=0.16), the ratio of urine calcium/urine creatinine (P=0.29), alkaline phosphatase (isoform bone) (P=0.3), procollagen-I-peptide (P=0.5), osteocalcin (P=0.9), serum phosphatase (P=0.71), parathormone (P=0.11) and the ratio urine phosphatase/urine creatinine (P=0.58) Therapy with ibandronate in patients with OI leads to a normalisation of bone turnover markers and increasing bone density. Therefore serum alkaline phosphatase and bone density are possible parameters to monitor bisphosphonate treatment in patients with OI.

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