Dental Implants in Osteoporotic Patients Taking Oral Bisphophonates: A Literature Review

Research Article

Austin J Dent. 2017; 4(3): 1071.

Dental Implants in Osteoporotic Patients Taking Oral Bisphophonates: A Literature Review

Nuti N*, Baldini N, D’Elia C, Gabriele G, Gennaro P and Ferrari M

Department of Medical Biotechnology, University of Siena, Italy

*Corresponding author: Niccolò Nuti, Department of Medical Biotechnology, University of Siena, Italy

Received: February 03, 2017; Accepted: March 14, 2017; Published: April 03, 2017

Abstract

Objective: Osteoporosis is a systemic disorder characterized by generalized decrease in bone mineral density that can eventually result in fragility fracture. Bisphosphonates have been used in the treatment of osteoporosis for many years in order to inhibit bone resorption. Unfortunately, the use of bisphosphonates has been found to be associated with several adverse events in patients where dental pathologies were present. For this reason, an increased attention has been recommended in those patients where bisphosphonates have been assumed and where dental therapies are mandatory. The aim of this article is to focus on the aspects of implant therapy in patients under bisphosphonates treatment and to produce a bibliographic review of dental implants placed in osteoporotic/osteopenic patients under treatment with oral bisphosphonates.

Materials and Methods: The literature review was performed on PUBMED, MEDLINE using as search terms: oral bisphosphonates, dental implants, osteoporosis/osteopenia, osteonecrosis of the jaws (ONJ).

Conclusions: In conclusion the analysis of the studies shows that the therapy with oral bisphosphonates does not affect osteointegration of dental implants and in most cases determines a low risk of ONJ.

Keywords: Oral bisphosphonates; Dental implants; Osteoporosis/ osteopenia; Osteonecrosis of the jaws (ONJ)

Introduction

Osteoporosis is a systemic skeletal disorder characterized by skeletal fragility, and macro/micro-architectural modifications [1]. Osteoporosis is one of the most common chronic diseases referred in 1/3 postmenopausal women and 1/5, men over the age of 50 years (European Parliament Osteoporosis Interest Group and EU Osteoporosis Consultation Panel 2004) [2]. For example in Europe, the USA and Japan, osteoporosis is estimated to affect 75 million people [3] ; currently, it is estimated that over 200 million people worldwide suffer from this disease, and the incidence of osteoporosis increases exponentially after the age of 50 [4] . In fact one third of women and one-fifth of men over 50 had experienced osteoporotic fractures [5,6]. The risk of hip, forearm and vertebrae fracture is approximately 40% the same as the risk of cardiovascular disease [6]. According to some authors, 40% of women [7,8] or 50% of women over 50 [9] and up to 29% of men may sustain an osteoporotic fracture. A higher prevalence of fragility fractures has been described in white populations [10], especially in non Hispanic-Caucasians [11]; lower rates have been found among black populations [10]. In Europe, the Scandinavian countries have the highest prevalence of fragility fractures [12]. Although it is widely recognized that low bone mass is not the only determinant of bone fragility, the strength of the skeleton is influenced by other bone tissue properties, collectively named “bone quality” [13,14]. The mean change of bone remodelling pattern in osteoporosis patients resulted in perforation of trabecular plates and loss of cancellous trabecular elements with consequent bone mineral density. Established risk factors for osteoporosis include older age; female gender; post-menopause; Caucasian or Asian race; a low body mass index; cigarette use; alcoholism; inadequate calcium and vitamin D intakes; physical inactivity; taking medications such as glucocorticoids and anticonvulsants; and anorexia nervosa [15,16].

The current medications approved for osteoporosis include calcium, vitamin D, bisphosphonates, parathyroid hormone, selective estrogen, receptor modulators, calcitonin, hormone therapy, denosumab and strontium ranelate [17]. Bisphosphonates drugs have now been in use for more than 10 years, and the number of patients who have used them or continue to use them is on the increase. These drugs are commonly prescribed to stabilize bone loss caused by osteoporosis in millions of postmenopausal women [18]. The term “bisphosphonates” is derived from the base of the drug, namely two phosphate (PO3) groups covalently linked to a central carbon. The carbon atom confers resistance to hydrolysis and allows two R sidechains to attach. The short side chain, R1 influences the chemical properties, whereas the long side chain R2 determines the mode of action and the strength of bisphosphonates. Bisphophonates inhibit osteoclasts by two mechanisms, depending on whether the R2 side chain contains nitrogen side groups. Bisphosphonates can be divided into two groups:

Bisphophonates are available in oral doses (daily, weekly, monthly and quarterly) and in intravenous yearly doses [17]. There are differences between bisphophonates administered intravenously and those taken orally.

Intravenous bisphosphonates

Intravenous bisphosphonates are antiresorptive medications used to manage cancer-related conditions including hypercalcemia of malignancy, skeletal-related events (SRE) associated with bone metastases in the context of solid tumors such as breast cancer, prostate cancer and lung cancers, and for the management of lytic lesions in the setting of multiple myeloma [19,20] While the potential for bisphosphonates to improve cancer-specific survival remains controversial, these medications have had a significant positive effect on the quality of life for patients with advanced cancer involving the skeleton.

Oral bisphosphonates

Oral bisphosphonates are approved for treatment of osteoporosis and are frequently used to treat osteopenia as well [21]. They are also used for a variety of less common conditions such as Paget’s disease of bone, and osteogenesis imperfecta [22,23]. The most common use, however, is for osteopenia and osteoporosis [24,25].

An increase in life expectancy of the world population has been observed [26,27]. Like osteoporosis, in this context, the edentulism affects the elderly population around the world (from 11% to 44%) [28]; US data show that the number of edentulous patients in 2020 will be around 38 million people [29]. The use of dental implants constitutes a well-documented treatment-modality [30] and represents an alternative to rehabilitate these patient aesthetically and functionally and present high predictability. Success becomes more predictable when adequate local and systemic conditions are present to provide bone healing during the osteointegration process [31,32]. Since the increase of life is accompanied inexorably with the greatest chance of having bone diseases, frequently in clinical practice we might treat osteoporotic subjects with dental implants. As written above most osteoporotic patients are taking oral bisphosphonates such as alendronate, risendronate or ibandronate. Bisphosphonates treatment was first identified by Marx in 2003 as a possible contributor to osteonecrosis of the jaw, a serious dental-medical complication that is seen among individuals undergoing invasive dental procedures such as extraction and implant placement [33]. Oral surgical procedures, including dental implant placements are known to be the most relevant risk factors for the ONJ development in cancer patients taking intravenous bisphosphonates; the majority of ONJ cases reported in the scientific literature after dental implants placement and oral surgery such as dental extraction include patients receiving intravenous bisphosphonates for bone metastases and multiple myeloma [34]. Furthermore, with the introduction of nBPs, namely zoledronate (zoledronic acid), which has a powerful bone resorption inhibitor, the incidence of complications associated with intra-venous BPs has grown [35,36]. The incidence of BRONJ after dental extractions range from 1% to 11% in breast cancer patients, 3% to 17% in multiple myeloma patients, and 3% to 18% in prostate cancer patients [37,38]. Kühl, et al. selected 23 studies and reported an incidence of BRONJ equal to 0-11.5% in therapies up to one year and 0-27.5% in therapies lasting from 1 to 4 years with the use of zoledronate [36]. The current guidelines contraindicate the use of dental implants in cancer patients taking intravenous bisphosphonates [39]. Mínguez-Serra, et al. [40] suggested the avoidance of dental implant procedures in patients that have been receiving intravenous BPs. This is in accordance with several studies where it has been shown that the combined use of oral and intravenous BP, have determined cases of osteonecrosis [41-43].

The estimated incidence of orally administered bisphosphonates related osteonecrosis of the jaws for patient treated with weekly alendronate is 0.01 to 0.04% [44]; furthermore, when administered intravenously, bisphosphonate loads bone and accumulates in bone 142.8 times faster than when administered orally [45]. For this reason, dental implant placement is not contraindicated in patients taking oral bisphosphonates, but oral surgical procedures are considered the major risk factor of development of ONJ in patients under therapy with this drugs [46]. The aim of this article is to produce a bibliographic review of dental implants placed in osteoporotic/ osteopenic patients under treatment with oral bisphosphonates.

Materials and Methods

According to our aim, a literature review was performed on PUBMED, MED-LINE using as search terms: oral bisphosphonates, dental implants, osteoporosis/osteopenia, osteonecrosis of the jaws. Our research discovered 166 papers of which these only 22, following the inclusion and esclusion criteria, were eligible for our literature According to our aim, a literature review was performed on PUBMED, MED-LINE using as search terms: oral bisphosphonates, dental implants, osteoporosis/osteopenia, osteonecrosis of the jaws. Our research discovered 166 papers of which these only 22, following the inclusion and esclusion criteria, were eligible for our literature review.

The inclusion parameters were:

The esclusion paramaters were:

Results

Following the inclusion and esclusion criteria, 22 papers were eligible for our literature review; we preferred to perform a literature review rather than a systematic review or meta-analysis because there were many variables in the studies that we have carefully selected, represented by the number of selected patients, the number of implants placed, the follow-up period and finally the type of drug taken by patients. In the selected studies, the main complication was represented by the osteonecrosis of the jaws (ONJ); in fact we have divided the studies into two tables. The first contains all studies where there has not been this kind of complication, in the second, where it is manifested.

Citation: Nuti N, Baldini N, D’Elia C, Gabriele G, Gennaro P and Ferrari M. Dental Implants in Osteoporotic Patients Taking Oral Bisphophonates: A Literature Review. Austin J Dent. 2017; 4(3): 1071. ISSN : 2381-9189