麻豆传媒

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

The teeth, although made of enamel and dentin, not bone, straddle both the skeletal system and the digestive system.

And while there are many reasons adults have early tooth loss, ranging from decay and infection to trauma, the loss of alveolar and mandibular/maxillary jaw bone is a major factor. Some research has suggested that early tooth loss may be a surrogate predictor for later development of osteoporosis at other sites.

For example, a of Indian women with a mean age of 55 found that average tooth loss was significantly higher in those with osteoporosis than in those with normal bone mineral density. Likewise, the odds of having osteoporosis among patients with three or more lost teeth was 4.2. The researchers concluded that tooth loss may be used as a proxy indicator to predict osteoporosis.

"Periodontal disease, which causes tooth loss and affects about half the world's population, may share a common underlying inflammatory pathway with osteoporosis. So it may well be a marker for osteoporosis," said June Sadowsky, DDS, a geriatric dentist with UTHealth Houston School of Dentistry, adding that both are chronic destructive diseases of bone.

She noted that the jaw has two kinds of bone – the alveolar, the top layer in which the teeth are embedded; and cancellous, which remains in the maxilla (upper jaw) and the mandible (lower jaw) after all alveolar bone is lost.

In addition to mobile teeth, salivary markers are also being considered as potential associative indicators of osteoporosis. For example, research has shown that salivary calcium and alkaline phosphatase were . "Hence, screening of salivary samples of patients may be an effective indicator for the detection of underlying disorders of bone metabolism," the investigators said.

Osteonecrosis of the Jaw

Delayed dental healing after bone-invasive procedures has been associated with long-term use of antiresorptive drugs (ARDs) such as bisphosphonates and denosumab, as well as antiangiogenic agents and receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitors. And, though rare, osteonecrosis of the jaw (ONJ) is a feared complication in both osteoporosis and cancer patients. Blood flow to the jaw bone is disrupted secondary to infection, which can also lead to sclerosis and death of bone tissue. ONJ can be treated successfully, however.

As the American Dental Association (ADA) notes, however, ONJ, though serious, is rare: the highest risk of drug-related ONJ was in a large sample of ARD-treated patients.

Still, said Sadowsky, "ONJ may not be common but if it happens to you it's 100% common."

Earlier research had posited a link between ONJ and long-term use of ARDs, including bisphosphonates and denosumab, after invasive oral procedures such as tooth extraction, root canal surgery, and dental implants. A 2006 retrospective for example, reported an eightfold increase in ARD-related ONJ risk with both IV and oral administration.

Evidence-based data now suggest, however, that the development of ONJ is a multifactorial process, said Kenneth E. Fleisher, DDS, of the College of Dentistry at New York University in New York City.

"Twenty years ago we saw ONJ primarily in cancer and osteoporosis patients given these drugs who wouldn't heal after tooth extractions. We made the jump to the conclusion that it was the extraction and the long half-life of bisphosphonates that were to blame for delayed healing and ONJ," he said. These drugs were thought to preferentially favor the jaw, which explained why they did not cause bone necrosis at other sites, he added.

Fleisher noted that while fewer than 1% of cancer and osteoporosis patients on these drugs develop ONJ, some individuals who have never taken antiresorptive medications do develop the condition, confounding the premise that these drugs directly cause ONJ.

Information from the ADA notes that 94% of is associated with these medications in cancer patients receiving repeated high doses through intravenous infusion for bone metastases. The remaining 6% receive much lower doses for treatment of osteoporosis.

Fleisher said he believes that medical comorbidities, infection, and specifically underlying osteomyelitis are the likely primary drivers of ONJ and delayed dental healing after oral surgery. Other risk factors are chemotherapy and poor oral hygiene.

The association with comorbidities is supported by a 2017 in which he and his colleagues concluded that ONJ and delayed dental healing were related to comorbidities and not to a history of antiresorptive therapy. He stressed the need for research into the effects of local microbial, inflammatory, and metabolic factors in the pathogenesis of ONJ and delayed healing.

Similarly, a study of in patients receiving bisphosphonates found that many already had osteomyelitis or osteonecrotic structural bone changes at the time of extraction -- an important consideration for understanding the different pathogenesis of ONJ.

Still, the role of drug holidays before oral surgery remains controversial, Fleisher said. "While it is not necessary to stop taking antiresorptives before dental surgery, physicians should discuss potential changes in medication with patients beforehand."

Dental Implants

A by the ADA said antiresorptive therapy is not a contraindication to dental implant placement. The statement stressed that in light of the morbidity and mortality of osteoporosis-related fractures, treatment with antiresorptive agents far outweighs the low risk of medication-related ONJ in patients with osteoporosis receiving these drugs.

The ADA acknowledges the need for large long-term studies to determine if implants placed in ARD-treated patients perform as well as those in unexposed patients. The organization identifies those at increased risk of ARD-related ONJ as receiving higher dosages and more frequent treatment schedules such as cancer patients, as well as those receiving the drugs for more than 2 years or having periodontitis or dentures.

Reducing Risk

In a an expert panel recommended a comprehensive program of sound oral hygiene practices and regular dental care for lowering ARD-related ONJ risk.

Furthermore, no validated diagnostic technique currently exists to determine which patients are at increased risk of developing the condition, nor is there sufficient evidence to recommend the use of serum biomarker tests such as serum C-terminal telopeptide to predict ONJ risk in patients receiving ARDs for osteoporosis.

A suggested that the incidence of ONJ can be reduced in cancer patients on ARDs with preventive dental interventions, and this finding is likely applicable to osteoporosis patients. These measures include completion of major dental treatment before commencing ARDs and the use of antibiotics before and after dental surgery. There are also data that the risk goes down during time off from the medication.

Sadowsky emphasized that good periodontal health is particularly important for people with low bone density: "If they have loose teeth or bleeding gums, they should seek dental care right away, and some may need to have more frequent professional cleanings every 2-3 months," she said.

These individuals should always brush after eating, floss thoroughly to remove the bacteria that cause inflammation and infection in the jaw bone, and never smoke, she added. "The earlier they get into good periodontal condition, the less risk they have that osteoporosis will cause problems in the mouth."

Read previous installments in this series:

Part 1: New Insights Into the Complex Biology of Osteoporosis

Part 2: The Latest on Osteoporosis Treatment and Diagnosis

Part 3: Osteoporotic Fragility Fractures

Part 4: Case Study: First-Time Mom's Severe Low Back Pain After Breastfeeding

Part 5: As Men Live Longer, Osteoporosis Looms Larger

Part 6: These Other Medical Conditions and Treatments Can Also Increase Osteoporosis Risk

Part 7: Talking to Patients About Osteoporosis

Part 8: Case Study: Shocking Development of Osteoporosis in a Teenager