Bisphosphonates: Pharmacokinetics, bioavailability, mechanisms of action, clinical applications in children, and effects on tooth development

Soares, Ana Prates; Santo, Renan Fernandes do Espírito; Line, Sérgio Roberto Peres; Pinto, Maria das Graças Farias; Santos, Pablo de Moura; Toralles, Maria Betânia Pereira; Santo, Alexandre Ribeiro do Espírito

doi:10.1016/j.etap.2016.01.015

Cited by 52 publications

(44 citation statements)

References 64 publications

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“…To control pediatric ODs, N-BPs were first used only in the 90s, with the application of pamidronate to treat osteogenesis imperfecta (OI) (Eghbali-Fatourechi, 2014). Nowadays, N-BPs are considered the first line in the management of most pediatric ODs (Baroncelli & Bertelloni, 2014;Eghbali-Fatourechi, 2014;Palomo, Vilaça, & Lazaretti-Castro, 2017;Soares et al, 2016) and are also indicated for other conditions, such as the recovery of bone mass and the reduction of fracture rates in bone disorders associated with immobilization (Baroncelli & Bertelloni, 2014;Eghbali-Fatourechi, 2014). The main N-BPs prescribed in pediatric patients are alendronate, pamidronate, and zoledronate (Baroncelli & Bertelloni, 2014;Eghbali-Fatourechi, 2014;Muderis, 2007) the last one being specifically used in the treatment of pediatric bone malignancies (Eghbali-Fatourechi, 2014).…”

Section: Main Clinical Applicationsmentioning

confidence: 99%

“…there are no standardized protocols for each condition (use and duration of therapy); their side effects in axial-appendicular and craniofacial skeletal growth and their impact in adulthood have not been extensively evaluated (Baroncelli & Bertelloni, 2014;Palomo et al, 2017;Soares et al, 2016); and the long-term safety of the drugs in childhood is unclear because of the pediatric physiological characteristics of bone remodeling (Baroncelli & Bertelloni, 2014;Palomo et al, 2017).…”

Section: Main Clinical Applicationsmentioning

confidence: 99%

“…In postmenopausal women, N-BPs decrease the risk of fracture at vertebral and non-vertebral sites, including hip fractures , Weinerman & Usera, 2015; they also prevent heterotopic ossification after total hip replacement surgery and improve subsequent mobility , and prevent ectopic calcification and ossification after spinal cord injuries . N-BPs are also used in adults to control several factors associated with bone metastasis (breast, prostate and lung cancer and multiple myeloma) (Coleman & McCloskey, 2011 protocols for N-BP use in adult ODs, although the ideal duration for N-BP treatments is unclear and selecting specific bisphosphonates is subject to the characteristics of the drugs, the evaluation performed of their response and the knowledge of potential undesirable effects (Soares et al, 2016). The main N-BPs prescribed in adults are zoledronate, risedronate, alendronate, and ibandronate (Weinerman & Usera, 2015).…”

Section: Main Clinical Applicationsmentioning

confidence: 99%

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Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

Vargas-Franco

Castañeda

Rédini

et al. 2018

Journal Cellular Physiology

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Bisphosphonates are considered the most effective drugs for controlling adult and pediatric osteolytic diseases. Although they have been used successfully for many years, several side effects, such as osteonecrosis of the jaw, delayed dental eruption, atypical femoral fracture, and alterations to the bone growth system, have been described. After an overview of nitrogenous bisphosphonate, the purpose of this article is to describe their mechanisms of action and current applications, review the preclinical and clinical evidence of their side effects in the skeleton ("what we know"), and describe current recommendations for preventing and managing these effects ("what we can do"). Finally, promising future directions on how to limit the occurrence of these side effects will be presented.

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Section: Main Clinical Applicationsmentioning

confidence: 99%

Section: Main Clinical Applicationsmentioning

confidence: 99%

Section: Main Clinical Applicationsmentioning

confidence: 99%

See 1 more Smart Citation

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

Vargas-Franco

Castañeda

Rédini

et al. 2018

Journal Cellular Physiology

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“…The BPs currently in clinical use (Pamidronate, Alendronate, Risedronate, and Zoledronic acid) contain nitrogen side chains that are thought to block the mevalonate pathway of sterol synthesis and interfere with post‐translational modifications of GTP‐binding proteins, which are essential for osteoclastic cytoskeletal function [Soares et al, ]. BPs can be administered either orally or intravenously.…”

Section: Therapeutic Interventions In Osteogenesis Imperfectamentioning

confidence: 99%

Pharmacological and biological therapeutic strategies for osteogenesis imperfecta

Marom¹,

Lee²,

Grafe³

et al. 2016

American J of Med Genetics Pt C

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Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility, low bone mass, and bone deformities. The majority of cases are caused by autosomal dominant pathogenic variants in the COL1A1 and COL1A2 genes that encode type I collagen, the major component of the bone matrix. The remaining cases are caused by autosomal recessively or dominantly inherited mutations in genes that are involved in the post-translational modification of type I collagen, act as type I collagen chaperones, or are members of the signaling pathways that regulate bone homeostasis. The main goals of treatment in OI are to decrease fracture incidence, relieve bone pain, and promote mobility and growth. This requires a multi-disciplinary approach, utilizing pharmacological interventions, physical therapy, orthopedic surgery, and monitoring nutrition with appropriate calcium and vitamin D supplementation. Bisphosphonate therapy, which has become the mainstay of treatment in OI, has proven beneficial in increasing bone mass, and to some extent reducing fracture risk. However, the response to treatment is not as robust as is seen in osteoporosis, and it seems less effective in certain types of OI, and in adult OI patients as compared to most pediatric cases. New pharmacological treatments are currently being developed, including anti-resorptive agents, anabolic treatment, and gene- and cell-therapy approaches. These therapies are under different stages of investigation from the bench-side, to pre-clinical and clinical trials. In this review, we will summarize the recent findings regarding the pharmacological and biological strategies for the treatment of patients with OI. © 2016 Wiley Periodicals, Inc.

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“…Bisphosphonates has been studied to suppress osteoporosis . However, there is a concern that suppressing the remodeling of bone could not avoid the jaw osteonecrosis . Therefore, a safer and more effective strategy for the treatment of osteoporotic injury and osteoporosis itself is needed.…”

Section: Introductionmentioning

confidence: 99%

Intra‐bone marrow injection of trace elements co‐doped calcium phosphate microparticles for the treatment of osteoporotic rat

Yang

Chen

et al. 2017

J Biomedical Materials Res

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Osteoporotic femur fractures are the most common fragility fracture and account for approximately one million injuries per year. Local intervention by intra-marrow injection is potentially a good choice for preventing osteoporotic bone loss when the osteoporotic femoral fracture was treated. Previously, it was shown that trace element co-doped calcium phosphate (teCaP) implants could stimulate osteoporotic bone marrow mesenchymal stem cell activity in vitro and bone regeneration in femoral bone defects in osteoporotic animal models. They hypothesized that local intra-marrow injection of teCaP particles could improve bone function because the teCaP can sustain release of biologically essential inorganic minerals and improve bone remodeling in osteoporosis. The teCaP and CaP particles were synthesized in simulated body fluid with and without adding silicon, zinc and strontium ions. Female rats (8 months) were ovariectomized (OVX) or sham-operated, and then intervened in the femoral marrow space at 12 months old. Groups include: (1) saline water; (2) CaP particles; and (3) teCaP particles. After 2-3 months of intervention, the sham groups showed higher bone mineral density (MBD) in the femur, and teCaP group increased the BMD in the OVX groups. The compressive strength of the OVX-teCaP group was significantly higher than that in the OVX-CaP group. Significant differences between OVX-teCaP and OVX-CaP groups were found for bone mineral microarchitecture, bone mineral density, and trace mineral content, but not for feces composition. These results confirm the teCaP particles could suppress osteoporotic bone loss by local intramarrow injection. Therefore, this biomaterial could be used as a next-generation combination treatment for osteoporotic trauma and osteoporosis itself. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1422-1432, 2017.

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Bisphosphonates: Pharmacokinetics, bioavailability, mechanisms of action, clinical applications in children, and effects on tooth development

Cited by 52 publications

References 64 publications

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

Pharmacological and biological therapeutic strategies for osteogenesis imperfecta

Intra‐bone marrow injection of trace elements co‐doped calcium phosphate microparticles for the treatment of osteoporotic rat

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