Can the alendronate dosage be altered when combined with high-frequency loading in osteoporosis treatment?

Correa, CB; Camargos, G V; Chatterjee, Marissa; Mesquita, MF; Cury, AA Del Bel; Naert, Ignace; Duyck, Joke; Vandamme, Katleen

doi:10.1007/s00198-016-3859-1

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…The ovariectomized rat model has been widely used to evaluate the effects of drugs in osteoporosis (Correa et al, 2016). Similarly, the zebrafish is an ideal vertebrate model for studying the toxicity of various drug therapies in tumor angiogenesis and bone formation (Zhang L.I.…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats

Zhong

Wang

et al. 2017

Front. Pharmacol.

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Xian-ling-gu-bao (XLGB) is a well-known patented traditional Chinese prescription widely used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, or climacteric syndrome. However, recent reports have suggested that XLGB may cause liver injury in humans. In the present study, we aimed to evaluate the efficacy of XLGB in the prevention of osteoporosis in the zebrafish and ovariectomized (OVX) rats, both of which have been used as osteoporosis models. The safety of XLGB after long-term administration to OVX rats was also assessed. OVX rats were administered by oral gavage 270 mg/kg (recommended daily dose), 1350 mg/kg, and 1800 mg/kg of XLGB for 26 weeks. Bone mineral density, relative bone surface to bone volume, relative bone volume to total volume, trabecular number, mean trabecular thickness, and mean trabecular spacing in OVX rats were examined at the end of the 26-week dosing period. Additionally, OPG and RANKL expression in the femur were determined by western blot and immunohistochemical staining. To evaluate the safety of XLGB, body weight, hematology, serum biochemistry markers related to toxicology, and organ histopathology were determined in each group of OVX rats. Conversely, the zebrafish was treated with prednisolone to induce osteoporosis in the embryo. Disodium etidronate was used as a treatment control. XLGB was shown to be effective in preventing osteoporosis in both the OVX rats and the prednisolone-treated zebrafish. Similarly, XLGB increased OPG protein and decreased RANKL protein in OVX rats. Interestingly, no obvious toxicity was observed in the heart, liver, kidney, small intestine, or stomach at dosages of up to 1800 mg/kg after treating the OVX rats for 26 weeks. XLGB was shown to be very effective in treating osteoporosis in OVX rats. No obvious toxicity or adverse effects developed in OVX rats at dosages up to 1800 mg/kg, which is equivalent to six times the daily-recommended dose. Therefore, XLGB should be considered a good option for the treatment of post-menopausal osteoporosis.

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Section: Introductionmentioning

confidence: 99%

Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats

Zhong

Wang

et al. 2017

Front. Pharmacol.

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“…In humans, patients with rheumatoid arthritis [38, 39] after treatment with steroids also were observed to have increases in the endocortical perimeter. Also, exercise in men [36] and high-frequency loading have been shown to increase the trabecular area and endocortical perimeter [7]. With the numbers of patients we had, we could not detect a difference in cortical porosity between patients who were treated for osteosarcoma and the control group.…”

Section: Discussionmentioning

confidence: 94%

Is There an Association Between Bone Microarchitecture and Fracture in Patients who were Treated for High-grade Osteosarcoma? A Controlled Study at Long-term Follow-up Using High-resolution Peripheral Quantitative CT

Holzer

Hobusch

Hansen

et al. 2021

Clin Orthop Relat Res

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Background Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect. Questions/purposes (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma? Methods We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals. Results Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity. Conclusion Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture. Level of Evidence Level III, therapeutic study.

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“…Umgekehrt kann auch eine mechanische Überbelastung bei richtig und kurz dosierter Bisphophonat-Therapie eine negativen Effekt hervorrufen [38]. Additive Effekte bei korrekter Applikation von Medikamenten und angemessener Trainingsintensität wurden auch in präklinischen Modellen nicht gefunden [39,40]. Die präklinischen Szenarien würden also dafür sprechen, dass prinzipiell der anabole Effekt von Training auf die Knochenformation und damit die Knochendichte durch Bisphosphonate nicht verhindert wird, allerdings der durch Remodeling bedingte Anteil nicht stattfinden kann.…”

Section: Diskussionunclassified

Effekt von additivem körperlichem Training zur Bisphosphonat-Therapie auf die Knochendichte: Eine systematische Übersichtsarbeit und Meta-Analyse

et al. 2022

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Zusammenfassung Hintergrund Körperliches Training und antiresorptive pharmakologische Therapie wirken über unterschiedliche Mechanismen auf den Knochenstoffwechsel ein. Die vorliegende Arbeit beschäftigt sich mit dem Ansatz, ob eine Bisphosphonat-Behandlung durch zusätzliches körperliches Training additive Effekte auf die Knochendichte (BMD) an Lendenwirbelsäule (LWS) und/oder Schenkelhals (SH) ausübt. Methoden Unsere systematische Literaturrecherche von fünf elektronischen Datenbanken gemäß PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) schloss kontrollierten Studien mit einer Dauer von mehr als 6 Monaten und mindestens zwei Studienarmen: (a) Bisphosphonate (B), (b) Bisphosphonate und körperliches Training (B+E) bis zum 26. August 2021, ein. Studien mit anderen pharmazeutischen Therapien oder Krankheiten mit relevanten Auswirkungen auf den Knochenstoffwechsel wurden ausgeschlossen. Die vorliegende Analyse wurde als random-effects Meta-Analyse durchgeführt. Ergebnismaße waren standardisierte mittlere Differenzen (SMD) für BMD-Änderungen an LWS und Schenkelhals (SH). Ergebnisse Unsere Suche identifizierte vier geeignete Studien mit insgesamt 247 Teilnehmern. Zusammenfassend zeigte die kombinierte Intervention (B+E) verglichen mit der isolierten Bisphosphonat-Therapie keine signifikant höheren Effektstärken an LWS (SMD: 0,66, 95%-CI: − 0,63 bis 1,94) oder SH-BMD (0,49 − 0,42 bis 1,40). Wir beobachteten für beide Studienendpunkte (BMD-LWS, BMD-SH) eine sehr hohe Heterogenität der Ergebnisse der eingeschlossenen Studien (I2: 89 bzw. 92%). Die Wahrscheinlichkeit eines „small study“ bzw. Publikations-Bias liegt in beiden Fällen ebenfalls recht hoch. Schlussfolgerung Wir konnten keinen signifikant überlegenen Effekt einer kombinierten Intervention aus Bisphosphonaten und körperlichem Training im Vergleich zu isolierter Bisphosphonat-Therapie auf die BMD an LWS oder SH erfassen. Allerdings zeigten die vorliegenden Einzelstudien eine hohe Heterogenität, die wir primär auf unterschiedlichen Trainingsprotokolle der Studien zurückführen. Schlüsselworte körperliches Training, Bisphosphonate, Knochendichte, Meta-Analyse

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Can the alendronate dosage be altered when combined with high-frequency loading in osteoporosis treatment?

Abstract: The bone anabolic potency of HF loading was overruled by the ALN dosages applied in the present study. Further altering the ALN dosage combined with robust mechanical stimuli needs to be considered in osteoporosis research and eventually therapy.

Cited by 4 publications

References 30 publications

Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats

Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats

Is There an Association Between Bone Microarchitecture and Fracture in Patients who were Treated for High-grade Osteosarcoma? A Controlled Study at Long-term Follow-up Using High-resolution Peripheral Quantitative CT

Effekt von additivem körperlichem Training zur Bisphosphonat-Therapie auf die Knochendichte: Eine systematische Übersichtsarbeit und Meta-Analyse

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