Clinical Review


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New guidance on benefits and risks of bisphosphonate therapy; a novel, food-friendly bisphosphonate formulation; and the risk of fracture in users of proton-pump inhibitors



We, and our patients, are fortunate to have a robust armamentarium of osteoporosis preventives and treatments in the 21st century. Still, we have much to learn about the preservation and restoration of bone. Fine-tuning of individual therapies, and clarification of their attendant risks, are ongoing concerns.

In this article, I highlight several recent studies:

  • an assessment of the periodontium in a group of postmenopausal women who were long-term users of bisphosphonates, versus nonusers, to determine the effects of these agents on periodontal health
  • guidance from the American Society for Bone and Mineral Research on the risk of atypical femoral fracture in long-term users of bisphosphonates
  • 2-year data on a new, delayed-release, weekly formulation of risedronate that can be taken with food
  • two meta-analyses exploring the risk of fracture with use of a proton-pump inhibitor (PPI), as well as a recent summary of evidence
  • a randomized trial of 2% nitroglycerin ointment to prevent fracture.

Bisphosphonates may reduce the risk of postmenopausal periodontal disease

Palomo L, Buencamino-Francisco MC, Carey JJ, Sivanandy M, Thacker H. Is long-term bisphosphonate therapy associated with benefits to the periodontium in postmenopausal women? Menopause. 2011;18(2):164–170.

The risk of periodontal disease increases in menopause. Inflammation can erode structures (i.e., periodontal ligament and alveolar bone) that attach the teeth into the jaw, leading, eventually, to loss of teeth (FIGURE).

Anatomy of healthy periodontium
In periodontal disease, inflammation can erode structures, such as the periodontal ligament and alveolar bone, that attach the teeth into the jaw.In periodontal inflammation, a bacterial biofilm on tooth surfaces triggers a response by neutrophils and macrophages. In this respect, osteoporosis and periodontitis are mediated by common cytokines. Local production of cytokines seems to enhance osteoclast-mediated loss of skeletal and alveolar bone in estrogen-deficient women. In addition, generalized bone loss in postmenopausal osteoporosis renders the jaw susceptible to accelerated alveolar bone resorption and loss of periodontal attachment. For these reasons, physicians who care for postmenopausal women are advised to monitor their periodontal health; be vigilant for dental problems; and encourage them to practice good oral hygiene as a preventive measure against periodontitis and to seek regular dental care.

There has been tremendous publicity about the rare but very serious occurrence of osteonecrosis of the jaw in women who use bisphosphonates. In contrast, this study by Palomo and colleagues from the Case Western Reserve School of Dental Medicine seems to offer some preliminary good news about bisphosphonates and dental health: Long-term use appears to have some beneficial effects on the periodontium of postmenopausal women.

Details of the study

The aim of the study was to compare the periodontium in two groups of postmenopausal women known to have low bone mineral density (BMD): those who were long-term users (>2 years) of bisphosphonate therapy (n=28) and those who were not (n=28). The average age of participants in the study was 63 years, and the average T-score was –2.5. All women underwent cone-beam computed tomography of the jaw and a complete periodontal examination to determine the plaque score, periodontal probing depth, clinical attachment loss, bleeding on probing, and alveolar bone height.

Findings: Bisphosphonate users had a higher plaque score, a lower probing depth, and less loss of clinical attachment than did women in the control group. These differences were determined to be statistically significant. Bisphosphonate users also had less bleeding on probing and a higher alveolar bone height, but these differences were not significant. After adjustment for the plaque score, bisphosphonate use was a significant factor for probing depth but not for the other parameters.


Not all news about bisphosphonates is bad. Preliminary data seem to indicate that objective measures of periodontal disease are lower in bisphosphonate users who have low BMD than in nonusers.

Atypical femoral fracture is a real risk—but a rarity—with long-term use of antiresorptive drugs

Shane E, Burr D, Ebeling PR, et al; American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010;25(11):2267–2294.

As ObGyns, we are often the first-line providers of diagnostic services and treatment for postmenopausal women at risk of osteoporotic fracture. Oral and, more recently, parenteral bisphosphonates have been a mainstay of such treatment. Isolated reports of atypical femoral fracture in long-term users of bisphosphonates first surfaced around 2005.1 Since then, several case series have appeared, some with as many as 102 cases.2 In fact, atypical femoral fracture in bisphosphonate users has drawn so much attention that patients have begun to ask about these agents and express reservations about using them.


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