Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review

Paulo, Siri; Abrantes, Ana Margarida; Laranjo, Mafalda; Marto, Carlos Miguel; Paula, Anabela; Trancoso, Pedro; Botelho, Filomena; Serra, Arménio; Ferreira, Manuel Marques

doi:10.3390/jfb17030145

Open AccessReview

Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review

by

Siri Paulo

^1,2,*

,

Ana Margarida Abrantes

^2,3,4,5,6

,

Mafalda Laranjo

^2,3,4,5

,

Carlos Miguel Marto

^{2,3,4,5,7,8,9}

,

Anabela Paula

^2,3,4,7,9

,

Pedro Trancoso

^10,11,

Filomena Botelho

^2,3,4,5,6

,

Arménio Serra

¹² and

Manuel Marques Ferreira

^1,2,4,9,13

¹

Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

²

Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal

³

Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal

⁴

Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-354 Coimbra, Portugal

⁵

Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

⁶

Medical Imaging and Radiotherapy Department, Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, 3046-854 Coimbra, Portugal

⁷

Institute of Integrated Clinical Practice, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

⁸

Institute of Experimental Pathology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

⁹

Laboratory for Evidence-Based Sciences and Precision Dentistry, University of Coimbra, 3000-548 Coimbra, Portugal

¹⁰

Egas Moniz School of Health & Science, Department of Oral Surgery and Oral Medicine, Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal

¹¹

Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal

¹²

Department of Chemical Engineering, Faculty of Sciences and Technology, University of Coimbra, 3030-790 Coimbra, Portugal

¹³

CEMMPRE—Centre for Mechanical Engineering, Materials and Processes, Chemical Engineering Department, University of Coimbra, 3000-548 Coimbra, Portugal

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J. Funct. Biomater. 2026, 17(3), 145; https://doi.org/10.3390/jfb17030145

Submission received: 8 February 2026 / Revised: 11 March 2026 / Accepted: 11 March 2026 / Published: 16 March 2026

(This article belongs to the Section Dental Biomaterials)

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Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is characterized by exposed necrotic bone that often progresses with increasing pain and impaired quality of life. Zoledronate, the most potent and widely used bisphosphonate, has been strongly associated with BRONJ development following invasive dental procedures. Given the rising incidence of BRONJ, understanding and implementing effective preventive strategies have become imperative. Biomaterials based on synthetic hydroxyapatite and beta-tricalcium phosphate have been investigated as potential preventive agents. Their therapeutic rationale is supported by two key principles: the well-documented chemical interaction of calcium phosphates with bisphosphonates when used as drug carriers, and the established clinical use of synthetic calcium phosphate biomaterials in dentistry for bone regeneration. This review examines the underlying mechanisms of this preventive therapeutic strategy and evaluates studies investigating synthetic calcium phosphate biomaterials for BRONJ prevention through zoledronate adsorption at jaw wound sites, thereby reducing soft tissue toxicity and promoting healing. The evidence supports the protective effect of these biomaterials as a scientifically grounded preventive approach for BRONJ.

Keywords: bisphosphonates; osteonecrosis of jaw; prevention; calcium phosphate; bone substitutes; synthetic biomaterials

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MDPI and ACS Style

Paulo, S.; Abrantes, A.M.; Laranjo, M.; Marto, C.M.; Paula, A.; Trancoso, P.; Botelho, F.; Serra, A.; Ferreira, M.M. Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review. J. Funct. Biomater. 2026, 17, 145. https://doi.org/10.3390/jfb17030145

AMA Style

Paulo S, Abrantes AM, Laranjo M, Marto CM, Paula A, Trancoso P, Botelho F, Serra A, Ferreira MM. Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review. Journal of Functional Biomaterials. 2026; 17(3):145. https://doi.org/10.3390/jfb17030145

Chicago/Turabian Style

Paulo, Siri, Ana Margarida Abrantes, Mafalda Laranjo, Carlos Miguel Marto, Anabela Paula, Pedro Trancoso, Filomena Botelho, Arménio Serra, and Manuel Marques Ferreira. 2026. "Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review" Journal of Functional Biomaterials 17, no. 3: 145. https://doi.org/10.3390/jfb17030145

APA Style

Paulo, S., Abrantes, A. M., Laranjo, M., Marto, C. M., Paula, A., Trancoso, P., Botelho, F., Serra, A., & Ferreira, M. M. (2026). Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review. Journal of Functional Biomaterials, 17(3), 145. https://doi.org/10.3390/jfb17030145

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Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review

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