Considerations in the use of antiresorptive agents, new treatment options, and a call to action
In the previous two installments of our Bone Health Lifetime Challenge series on issues surrounding bone mass accrual and osteoporosis in older adult fragility fracture patients, we addressed, in part one, nutrition, supplementation, and activity, and in part two, diagnosis and treatment. Here in part three, we discuss two potential adverse reactions to antiresorptive agents. Most commonly, these have been reported in studies of long-term bisphosphonate (BP) use. We conclude with a call for efforts to close the osteoporosis treatment gap, with orthopaedic surgeons taking the lead in promoting the bone health of all of our patients and the population at large.
Osteonecrosis of the jaw
Osteonecrosis of the jaw (ONJ) has been recognized for more than a decade but has been most predominantly associated with the use of antiresorptive agents for the treatment of metastatic malignancies in the skeleton. A recent review by a task force of the American Society for Bone and Mineral Research (ASBMR) notes that most dentists do not feel the cessation of BP treatment is necessary prior to dental procedures. The incidence range of ONJ is between 1/10,000 and 1/100,000 patient years, with no clear evidence of an increased incidence with prolonged medication use.
Atypical femur fractures
Atypical femur fractures (AFFs) have garnered significant attention from the orthopaedic community and the public since their identification nearly a decade ago in studies of patients who had used BPs for extended periods of time. Occurring usually in the subtrochanteric or femoral shaft region, they may be bilateral and often are associated with thigh pain. Characteristically, they have four of five major diagnostic criteria: minimal trauma; a fracture occurring at the lateral cortex with a primarily transverse orientation; complete fractures extending through both cortices, often with a medial bone spike; localized periosteal cortical thickening; and minimal comminution. Bilaterality is not uncommon; therefore, radiographic evaluation of both femurs is necessary. MRI is often necessary for diagnosis in the presence of symptoms with a normal radiograph.
While a number of AFFs with symptoms only or incomplete fracture lines may be treated nonsurgically, with assisted ambulation using a walker or cane, they necessitate close follow-up. The presence of a complete nondisplaced fracture, with radiographic evidence of the "dreaded black line," requires intramedullary fixation, as is the case for displaced fractures. According to the recent ASBMR task force review mentioned above, these atypical fractures, which may be associated with other diseases such as hypophosphatasia and, on occasion, also may involve the humerus, are quite rare. They occur at the rate of about 1/50,000 in patients using BPs for 2 years compared with about 110/100,000 patients in those using BPs for 8 to 10 years.
These findings have led to the current recommendation for women who are not at high risk for fracture to cease BP treatment after 5 years of oral BP use or 3 years of intravenous BP, with the initiation of a 2- to 3-year drug holiday. Given the fact that BPs reside in the skeleton for decades, this cessation of treatment does seem reasonable. Nevertheless, patients should have a dual x-ray absorptiometry (DXA) bone mass evaluation and possibly serum and urine bone markers obtained at that time since some with very severe osteoporosis may benefit from a more extended treatment duration.
In the coming years, we can expect new osteoporosis drugs to be available, including those that further reduce osteoclast function, such as cathepsin K inhibitors (odanacatib), and additional anabolic agents such as those that stimulate the Wnt pathway via sclerostin inhibition (romosozumab). Another anabolic agent is an analog of human PTH-related protein (abaloparatide) that can be administered by subcutaneous injection or transdermal patch. Other drugs in development target FGF-23 in patients with metabolic bone disease associated with chronic kidney disease, while other agents are designed to reverse sarcopenia.
Since vertebral fractures are extremely common—they are the most frequent of fragility fractures—it should be noted that their identification is often challenging, as they may not produce an acute pain episode. Nevertheless, because patients with osteoporotic vertebral fractures have a 4 to 5 times greater risk of additional fracture compared to the general population, all identified patients do need osteoporosis treatment. In addition, the spine literature now has well-regarded meta-analyses that indicate the benefit of kyphoplasty and vertebroplasty in appropriate patients with acute, painful fractures that do not respond to an early conservative treatment regimen. These facts also have prompted a greater appreciation and understanding of the osteoporotic vertebral fracture problem in the neurosurgical spine community.
For a review of the osteoporosis problem in general and specific treatment alternatives, the National Osteoporosis Foundation's (NOF) Clinician's Guide to Prevention and Treatment of Osteoporosis (revised 2014) has been an excellent resource for years and can be easily accessed online at https://my.nof.org/bone-source
The osteoporosis treatment gap
It is clearly time for orthopaedic surgeons to assist in closing that osteoporosis treatment gap, in order to prevent future fractures for their patients. This can be done through a Fracture Liaison Service of some sort, commonly led by an advance practice provider to coordinate the care of older adult fracture patients in concert with the orthopaedic surgeon, the primary care physician, and osteoporosis specialists as needed. This model, originally popularized in the United Kingdom, may take many different forms depending on the current practice setting for the orthopaedist and available medical colleagues. Here the American Orthopaedic Association's Own the Bone quality improvement program, for secondary fracture prevention, provides one answer. While this model was originally designed for inpatient use in those patients hospitalized for fracture care, it certainly can also be employed in an outpatient clinic setting. In addition, an FLS may be part of a more formal geriatric fracture program addressing the entire perioperative care spectrum of these patients.
Regardless of the method employed, the orthopaedic surgery community must continue to assume further leadership in this musculoskeletal arena by recognizing the challenge before us and promoting the bone health of all of our patients and the population at large.
Andrew D. Bunta, MD, is on the faculty of Northwestern University Feinberg School of Medicine, Chicago, and is chair of the AOA Own the Bone Multidisciplinary Advisory Board. Joseph M. Lane, MD, is professor of Orthopaedic Surgery and chief of the Metabolic Bone Disease Service, Hospital for Special Surgery, New York, N.Y.