OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Brett A. Freedman, MD, in response to a study published in JAMA about a new agent to prevent fractures in postmenopausal women with osteoporosis.
The August 16, 2016 issue of JAMA published the results of the ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial. This 28-site randomized trial allocated postmenopausal women with low bone mineral density (BMD) and/or a prior fragility fracture into one of three arms: abaloparatide (80 µg subcutaneously, daily ) vs. daily placebo injection vs. teriparatide (20 µg subcutaneously, daily). The primary end point was new vertebral fracture over the 18-month trial.
As expected, both anabolic agents significantly outperformed placebo, with incident vertebral fractures occurring in only 4 subjects in the abaloparatide arm (0.6%) and 6 in the teriparatide arm (0.8%), while there were 30 in the placebo arm (4.2%). Although the study was not powered to evaluate differences between the two anabolic agents, the results suggest that abaloparatide and teriparatide performed essentially the same over the 18-month period.
In an accompanying commentary,1 Cappola and Shoback note that institutional review boards (IRBs) approved a prospective clinical trial protocol in which patients with known osteoporosis and/or a prior fragility fracture were allowed to be randomized to a non-treatment arm for 18 months. Subjects whose BMD dropped more than 7% from baseline and those who experienced an incident fracture during the trial “were offered an option to discontinue and receive alternative treatment,” but in some sense IRB approval of this protocol implicitly acknowledged that osteoporosis is undertreated.
Turning back to the study itself, I noted with interest that subjects who had regularly used bisphosphonates in the last 5 years or denosumab in the last year were excluded. So, none of the 2463 subjects who were randomized had received any active treatment for osteoporosis in the 1 to 5 years prior to enrollment, despite the fact that the average T-score in the lumbar spine (-2.9 for all 3 arms) was in the osteoporotic range and that almost one-third of subjects had had at least one prior fragility fracture.
This is a sad commentary on “our” (meaning all providers involved in bone health) continued inability to diagnose and treat osteoporosis effectively. Despite the “National Bone and Joint Health Decade” (2002-2011) and our continued attempts to “Own the Bone,” we have made little progress in recognizing and treating the osteoporosis underlying the fragility fractures that we so frequently treat. Colleagues of mine and I published that only 38% of patients in 2002 with clinically diagnosed vertebral compression fragility fractures were receiving active treatment for osteoporosis.2 Over the ensuing decade, Solomon et al. showed that that figure actually decreased to 20%.3
This JAMA study provides empiric Level-I support for the efficacy of another anabolic agent to treat osteoporosis. Cost, subcutaneous delivery, and osteosarcoma concerns have limited the only FDA-approved anabolic osteoporosis medication, teriparatide, to second-line status, behind bisphosphonates. If and when approved, abaloparatide will probably bump up against the same limitations. Still, the parathyroid hormone receptor agonists are particularly pertinent to orthopaedic surgeons, because they are the most effective secondary fracture prevention agents—and the only ones that show meaningful improvement in bone mineral density. This bone-building property has also led to progressive acceptance of teriparatide as an important perioperative adjunct for instrumented spinal fusion surgery in patients with known osteoporosis.
However, as has been repeatedly shown, parathyroid receptor agonists only work when they are prescribed, and they are only prescribed when osteoporosis is diagnosed.2,3 Patients with incident clinical fragility fractures need to be effectively educated about osteoporosis, its treatment, and the impact of failing to treat it. Orthopaedic surgeons need to continue to set the signal flares and advocate for our patients to receive effective treatment for all their chronic musculoskeletal illnesses, not the least of which is osteoporosis.
- Cappola AR, Shoback DM. Osteoporosis Therapy in Postmenopausal Women With High Risk of Fracture. JAMA. 2016 Aug 16;316(7):715-6.
- Freedman BA, Potter BK, Nesti LJ, Giuliani JR, Hampton C, Kuklo TR. Osteoporosis and vertebral compression fractures-continued missed opportunities.Spine J. 2008 Sep-Oct;8(5):756-62.
- Solomon DH, Johnston SS, Boytsov NN, McMorrow D, Lane JM, Krohn KD. Osteoporosis medication use after hip fracture in U.S. patients between 2002 and 2011. J Bone Miner Res. 2014 Sep;29(9):1929-37.
Each month during the coming year, OrthoBuzz will bring you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators will highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.
“Injuries Involving the Epiphyseal Plate” by Drs. Salter and Harris, published more than a half-century ago, has had a lasting impact on the field of orthopaedic surgery and on the practice of medicine in general. Every surgeon in our specialty—and almost every radiologist, pediatrician, and emergency physician—has at least a passing knowledge of the “Salter fractures.” This most enduring orthopaedic schema lives on in our practices because of its clarity of presentation, its guidance of our understanding, and its implications for treatment. It has outlasted many classifications developed before and since.
In addition to presenting the fracture classification in this classic and beautifully illustrated JBJS Instructional Course Lecture, the authors laid the groundwork with basic principles of mechanical failure and vascularity of the physis. The authors then use these principles to help explain how physeal damage may arise from misalignment, crushing, or vascular interruption. The authors elucidate these concepts further by presenting experimental studies of growth arrest, with resulting histology, and the effects of interpositional surgery. Salter and Harris then describe the famous five types of physeal injury and the clinical implications for treatment and prognosis.
Not content with generalities, the authors conclude with an extensive section describing the variations of physeal fractures in each long bone. The article is fun and inspiring to read because of the obvious fascination that the authors had in exploring the topic so completely. Rarely has experimental and clinical thought been so nicely interwoven. We don’t write that way now, and rarely if ever will we see a 36-page article in one of today’s orthopaedic journals; in many ways we are poorer for that.
Classification systems are highly cited and influential; they figure prominently in lists of top-cited orthopaedic articles. Those at the top earn this rank by their utility. This is just one of three monumental contributions by the late Dr. Salter of Toronto (along with introducing us to surgical reorientation of the acetabulum and to continuous passive motion). Please share your reactions to this classic article and its impact on you and your practice.
Paul Sponseller, MD
JBJS Deputy Editor for Pediatrics
Pelvic binders can provide lifesaving compression in patients with hemodynamically unstable pelvic injuries. But a report in the March 11, 2015 JBJS Case Connector by Auston et al. emphasizes that such binders may do more harm than good in patients who have acetabular fractures without hemodynamic instability or other pelvic injuries. Because first responders or community physicians often apply pelvic binders, the authors cite the need for clearer guidelines for these devices and updated training of early clinical caregivers regarding their use. Potential complications of binder use cited previously in the literature include pressure sores, damage to internal organs, and sciatic nerve palsy, and Auston et al. suggest additional ones.
The authors describe three cases in which patients who were hemodynamically stable were placed in a pelvic binder, either during transport or ED evaluation, following blunt trauma sustained in motor-vehicle accidents. All three patients had acetabular fractures but no other abdominal or pelvic injuries. The authors suggest that pelvic binders may contribute to the displacement of acetabular fractures, and although they saw no visible evidence of chondral damage during open reduction and internal fixation of the fractures, they express concern about occult chondral abrasion and possible damage to chondrocytes at the cellular level if binders are used inappropriately.
The authors therefore conclude that while pelvic binders play an important role in patients with severe pelvic ring injuries and hemodynamic instability, “in the setting of a displaced acetabular fracture, we cannot recommend placement of a pelvic binder, even for pain relief or splinting during evaluation or transportation.”
In last month’s Editor’s Choice, JBJS Editor in Chief Vern Tolo. MD, called for more concerted efforts among orthopaedists to link care of fragility fractures to evaluation and treatment of osteoporosis. Now, JBJS Reviews Editor in Chief Thomas Einhorn, MD, echoes Dr. Tolo’s message in reference to the May 2 JBJS Reviews article on managing patients with osteoporotic distal radial fractures:
According to Dr. Einhorn, “This must-read article provides a concise summary of how to advance the diagnosis and treatment of osteoporosis and fragility fractures. The authors explain the latest evidence about the ‘three main pillars’ of treatment of distal radial fractures in people with osteoporosis: primary prevention, acute management, and reduction of risk of future fractures. The strides made among US orthopaedists to recognize and manage osteoporosis with programs such as the American Orthopaedic Association’s ‘Own the Bone’ initiative have been commendable. However, on a global scale, our specialty is woefully behind in taking an aggressive approach toward prevention and treatment of osteoporosis.”
The article “Declining Rates of Osteoporosis Management Following Fragility Fractures in the U.S., 2000 through 2009” by Balasubramanian, et al. in the April 2, 2014 JBJS is a bit discouraging, but it will hopefully serve as a wake-up call for orthopaedic surgeons to re-engage with our patients to diagnose and treat previously undetected osteoporosis.
Fragility fractures–which primarily affect the vertebrae, hip, distal radius, or proximal humerus–are often the initial indication of osteoporosis in older individuals. For more than a decade, orthopaedic surgeons treating these fractures have been strongly encouraged to evaluate patients in this age group for the osteoporosis generally associated with these fractures. The American Orthopaedic Association (AOA) in 2005 began developing the Own the Bone program, specifically addressing the need to evaluate and treat osteoporosis, as well as the fracture, in these patients. The AOA has formed liaisons with several other national organizations to advance this program, and by late 2013, 44 states had hospitals implementing Own the Bone at their local institutions.
This article is sobering. Despite concerted efforts to link care of fragility fractures to evaluation and treatment of co-existing osteoporosis, these authors report an actual decrease in the rate of osteoporosis management for these patients. Only one-third of the women and one-sixth of the men in this retrospective cohort study were evaluated and treated according to current clinical guidelines.
This is an important public health issue. Despite the fact osteoporosis management involves non-operative treatment, it is essential that orthopaedic surgeons become more cognizant of the association between fragility fractures and osteoporosis treatment, and put in place a protocol to ensure that these patients are evaluated and treated for osteoporosis, as well as for the fracture. Osteoporosis may not be under the direct guidance of the orthopaedic surgeon, but the recognition of this potential problem is squarely within the practice scope of orthopaedists, who are well positioned to initiate secondary prevention measures for these older individuals.