The Impact of Bisphosphonates on the Osteoclast Cells of Osteogenesis Imperfecta Patients

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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The prognostic role of bone turnover markers in multiple myeloma patients: The impact of their assay. A systematic review and meta-analysis

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2015.05.001 ◽

2015 ◽

Vol 96 (1) ◽

pp. 54-66 ◽

Cited By ~ 7

Author(s):

Valentina Pecoraro ◽

Laura Roli ◽

Luca Germagnoli ◽

Giuseppe Banfi

Keyword(s):

Systematic Review ◽

Multiple Myeloma ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Meta Analysis ◽

Prognostic Role ◽

Turnover Markers ◽

The Impact

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Reversal of adverse effects of neoadjuvant chemotherapy on bone turnover in pre- and post-menopausal women with zoledronic acid

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.556 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 556-556

Author(s):

R. Aft ◽

M. Naughton ◽

K. Trinkuas ◽

M. Watson ◽

K. Weilbaecher

Keyword(s):

Zoledronic Acid ◽

Growth Factor ◽

Neoadjuvant Chemotherapy ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Mineral Density ◽

Menopausal Women ◽

Turnover Markers ◽

Post Menopausal ◽

The Impact

556 Background: Ovarian failure secondary to adjuvant chemotherapy is known to have an adverse effect on bone mineral density and to increase bone turnover markers. The effects of chemotherapy with growth factor support in the absence of hormonal changes have not been described. The impact of zoledronic acid on these changes was also explored. Methods: We evaluated bone turnover markers in 82 women undergoing neoadjuvant chemotherapy for localized stage II/III breast cancer at initial diagnosis prior to treatment and after 4 cycles of epirubicin (75mg/m2)-docetaxel (75mg/m2) with pegylated G-CSF support with or without zoledronic acid. 47% of patients were post-menopausal and all groups were balanced for other variables. Women were randomized to receive zoledronic acid 4 mg IV every 3 weeks concurrently with chemotherapy (n=41) versus no bisphosphonate treatment (n=41). Bone turnover markers included: urinary N-telopeptide (NTx), serum bone specific alkaline phosphatase (BAP)and osteocalcin (OSTEO). Results: Women, regardless of menopausal status, who received no bisphosphonate had statistically significant increases in NTx, from baseline after 3 months of neoadjuvant chemotherapy using multivariable mixed repeated measures (p=0.0213). Women who received zoledronic acid concurrently with neoadjuvant chemotherapy had statistically significant decreases in NTx (p<0.0001), BAP (p<0.0001) and OSTEO (p=0.0295) from baseline. This is the first demonstration that anthracycline-taxane chemotherapy with growth factor support increased bone turnover markers in both post-menopausal and pre-menopausal women independent of hormone therapy, radiation therapy and surgery. Conclusions: Neoadjuvant chemotherapy with anthracycline- taxane and growth factor support increased bone resorption markers in both post-menopausal and pre-menopausal women. Zoledronic acid given concurrently with each cycle of chemotherapy reversed this increase in bone turnover markers. No significant financial relationships to disclose.

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

Annals of Translational Medicine ◽

10.21037/atm.2017.s030 ◽

2017 ◽

Vol 5 (S2) ◽

pp. AB030-AB030

Author(s):

Amr Gouda ◽

Samia Temtamy ◽

Ola Ali ◽

Walaa Nazim ◽

Mona Aglan ◽

...

Keyword(s):

Bone Turnover ◽

Osteogenesis Imperfecta ◽

Bone Turnover Markers ◽

Treatment Monitoring ◽

Turnover Markers

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THE IMPACT OF REGULAR FOOTBALL TRAINING ON BONE TURNOVER MARKERS

Issues of Rehabilitation, Orthopaedics, Neurophysiology and Sport Promotion – IRONS ◽

10.19271/irons-000126-2020-33 ◽

2020 ◽

Vol 33 (33) ◽

pp. 31-40

Author(s):

Kacper Pajor ◽

Justyna Szpyt ◽

Agnieszka Turoń-Skrzypińska ◽

Iwona Rotter

Keyword(s):

Physical Activity ◽

Bone Turnover ◽

Bone Metabolism ◽

Bone Turnover Markers ◽

The Body ◽

Type I ◽

Physical Activity Monitoring ◽

Turnover Markers ◽

Football Training ◽

The Impact

Introduction The condition of the skeleton is important not only in the perspective of osteoporosis prevention, but also as a factor affecting the frequency of injuries excluding physical activity. Monitoring the impact of specific sports on osteoclasts and osteoblasts acitivity allows optimization of programming of physical activity limiting the risk of bone mineralization disorders. The review analyzes available papers on the impact of regular football training on skeletal physiology changes analyzed by measuring bone turnover markers in the body. Aim Determining the impact of regular football training on bone mass regulation by analyzing bone turnover markers. Material and methods PubMed and SPORTDiscus with Full Text databases were searched using the keyword combination “the name of team sport” + bone turnover. There is no clinical trials about bone turnover markers among handball, hockey, basketball and volleyball players in the available literature that meet the inclusion criteria, so the topic of the review was narrowed down to football (soccer). After applying the exclusion criteria, five studies were qualified. Results In the analyzed papers, the concentration of osteocalcin, N-terminal procollagen type I extension propeptide and C-terminal telopeptide of type I collagen in blood increased as a result of regular football training. In 3 papers statistically significant (p < 0.05) increases were noted. Conclusions Football training can stimulate bone metabolism, being an effective and attractive form of bone fracture prevention, regardless of your level of sport. Due to the limited availability of studies, there is a high need for further studies describing the impact of physical activity on bone metabolism.

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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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The Impact of Mild Autonomous Cortisol Secretion on Bone Turnover Markers

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa120 ◽

2020 ◽

Vol 105 (5) ◽

pp. 1469-1477 ◽

Cited By ~ 1

Author(s):

Shobana Athimulam ◽

Danae Delivanis ◽

Melinda Thomas ◽

William F Young ◽

Sundeep Khosla ◽

...

Keyword(s):

Bone Turnover ◽

Bone Metabolism ◽

Bone Turnover Markers ◽

Cushing Syndrome ◽

Adrenal Tumors ◽

Cortisol Secretion ◽

Increased Risk ◽

Autonomous Cortisol Secretion ◽

Turnover Markers ◽

The Impact

Abstract Context Several studies have reported increased risk of fragility fractures in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration. Objective To evaluate the effect of MACS on bone metabolism in patients with adrenal adenomas. Design Cross-sectional study with prospective enrollment, 2014-2019 Setting Referral center. Patients 213 patients with adrenal adenomas: 22 Cushing syndrome (CS), 92 MACS and 99 nonfunctioning adrenal tumors (NFAT). Main Outcome Measures Osteocalcin, procollagen I intact N-terminal (PINP), C-terminal telopeptide (CTX), sclerostin. Results Patients with CS demonstrated lower markers of bone formation compared with patients with MACS and NFAT (CS vs MACS vs NFAT: mean osteocalcin 14.8 vs 20.1 vs 21.3 ng/mL [P < 0.0001]; mean PINP 34.8 vs 48.7 vs 48.5 µg/L [P = 0.003]). Severity of cortisol excess was inversely associated with sclerostin (CS vs MACS vs NFAT: mean sclerostin 419 vs 538 vs 624 ng/L, [P < 0.0001]). In a multivariable model of age, sex, body mass index, cortisol, and bone turnover markers, sclerostin was a significant predictor of low bone mass in patients with MACS (OR 0.63 [CI 95%, 0.40–0.98] for each 100 ng/L of sclerostin increase). After adrenalectomy, osteocalcin, CTX, and sclerostin increased by a mean difference of 6.3 ng/mL, 0.12 ng/mL, and 171 pg/mL (P = 0.02 for all), respectively. Conclusions Lower sclerostin level in patients with MACS reflects a reduction in osteocyte function or number associated with exposure to chronic cortisol excess. Increase in bone turnover markers after adrenalectomy suggests restoration of favorable bone metabolism.

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