Advanced Practice Provider Corner: Imminent Fracture Risk

Authored by: E. Michael Lewiecki, MD, FACP, FACE, New Mexico Clinical Research and Osteoporosis Center and Editor of Osteoporosis International

A previous fracture increases the risk of subsequent fractures [1], even when the previous fracture is considered to be “traumatic” [2]. Since the correlation between prior fracture and future fractures is robust and at least partially independent of bone mineral density (BMD), a previous fracture is one of the clinical risk factors included in the FRAX algorithm to estimate the 10-year risk of major osteoporotic fracture and hip fracture.

The relationship between prior fracture and future fracture risk is time-dependent, with the risk of future fracture being greatest in the time soon after the previous fracture. This was recognized years ago [3, 4] and has recently received greater attention in medical literature [5, 6]. There are important clinical implications with what is now called “imminent fracture risk.”

A population-based cohort study was conducted using the Icelandic National Register in 18,872 men and women born between 1907 and 1935, with fractures documented in over 510,265 person-years [6]. Major osteoporotic fractures (MOF; i.e., hip, spine, humerus, distal forearm) occurred in 5,039 individuals, of whom 1,919 experienced a second MOF.

The risk of a second MOF was highest immediately after the first MOF, with the risk progressively diminishing over the time of follow-up, yet still higher than the population without a MOF. The risk of a second MOF after a first increased 5% for each advancing year of age. Factors that might account for imminent fracture risk include accelerated rate of bone loss associated with immobility following a fracture, impaired cognitive function with surgery and hospitalization, frailty, falls, and adverse effects of medications used in the immediate post-fracture period [5].

The time- and age-dependency of fracture risk after a prior fracture suggest urgency for evaluation of factors contributing to fracture risk and initiation of treatment to reduce that risk. Particular attention should be addressed to the prevention of falls. When pharmacological therapy is indicated, treatment with an agent with rapid onset of anti-fracture efficacy may be preferable to one with a slow onset of action. Most clinical trials have shown benefit, at least with reduction of vertebral fracture risk, within 12 months of starting treatment [5].

The sequence of therapy appears to be important [7]. For patients at very high risk of fracture, starting treatment with an osteoanabolic medication followed by an antiresorptive drug provides an opportunity to restore degraded skeletal microarchitecture first and then stabilize and enhance that effect [8, 9]. It is essential that osteoanabolic therapy is followed by an antiresorptive agent; if it is not, benefit is likely to be quickly lost [10]. In contrast, treatment with a potent antiresorptive medication followed by an osteoanabolic agent may result in delay, attenuation, or reversal of BMD effects [11, 12].

The current step-treatment approach mandated by some payers of healthcare services, with one or two trials of antiresorptive therapy required before osteoanabolic therapy is allowed, deserves reappraisal. Starting treatment with an osteoanabolic agent or a combination of osteoanabolic and antiresorptive therapy may be preferable in some high risk patients [7].

In summary, the occurrence of a fracture is a mandate for urgent medical attention. Given the very large osteoporosis treat gap [13] and evidence that hip fracture rates in the U.S. are higher than projected in recent years [14], we, the medical community, must do better. Strategies aimed at reducing the treatment gap and reducing osteoporosis health disparities include harmonization of clinical practice guidelines, better use of current medications with appropriate combinations and sequencing [7], development of new therapeutic agents, fracture liaison services [15], better understanding of the concept of bisphosphonate holidays [16], consideration of treat-to-target for osteoporosis [17], and knowledge sharing with teleconferencing to elevate the level of expertise of motivated healthcare professionals in underserved communities [18].

More data are needed to evaluate the effectiveness of such strategies and the comparative effectiveness of pharmacological and non-pharmacological interventions for reducing imminent fracture risk. At the same time, physicians must continue to be vigilant in identifying, evaluating, and treating high risk patients before the first fracture occurs.

References

1.   Gehlbach S, Saag KG, Adachi JD, Hooven FH, Flahive J, Boonen S, et al. Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women. J Bone Miner Res. 2012;27(3):645-53.
2.   Mackey DC, Lui LY, Cawthon PM, Bauer DC, Nevitt MC, Cauley JA, et al. High-trauma fractures and low bone mineral density in older women and men. JAMA. 2007;298(20):2381-8.
3.   Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001;285:320-3.
4.   Johnell O, Oden A, Caulin F, Kanis JA. Acute and long-term increase in fracture risk after hospitalization for vertebral fracture. Osteoporosis International. 2001;12(3):207-14.
5.   Roux C, Briot K. Imminent fracture risk. Osteoporos Int. 2017;28(6):1765-9.
6.   Johansson H, Siggeirsdottir K, Harvey NC, Oden A, Gudnason V, McCloskey E, et al. Imminent risk of fracture after fracture. Osteoporos Int. 2017;28(3):775-80.
7.   Cosman F, Nieves JW, Dempster DW. Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis. J Bone Miner Res. 2017;32(2):198-202.
8.   Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Valter I, et al. Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial. Mayo Clin Proc. 2017;92(2):200-10.
9.   Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;Epub.
10.     Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. NEnglJ Med. 2005;353(6):555-65.
11.     Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, et al. Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res. 2008;23(10):1591-600.
12.     Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015;386(9999):1147-55.
13.     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;29(9):1929-37.
14.     Lewiecki EM, Adler RA, Curtis JR, Gagel R, Saag KG, Singer AJ, et al. Hip fractures and declining DXA testing: at a breaking point? J Bone Miner Res. 2016;31(Suppl):S26.
15.     National Bone Health Alliance. Fracture Prevention Central 2016 [updated March 28, 2016March 28, 2016]. Available from: www.nbha.org/fpc
16.     Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, et al. Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31(1):16-35.
17.     Cummings SR, Cosman F, Lewiecki EM, Schousboe JT, Bauer DC, Black DM, et al. Goal-Directed Treatment for Osteoporosis: A Progress Report From the ASBMR-NOF Working Group on Goal-Directed Treatment for Osteoporosis. J Bone Miner Res. 2017;32(1):3-10.
18.     Lewiecki EM, Boyle JF, Arora S, Bouchonville MF, 2nd, Chafey DH. Telementoring: a novel approach to reducing the osteoporosis treatment gap. Osteoporos Int. 2017;28(1):407-11.