Vertebral fractures (VFs) are one of the most common fragility fractures, conferring a two- to four-fold increased risk of subsequent hip fracture independent of bone mineral density (BMD). At a scientific symposium, Dr Ronald Man-Yeung Wong, Clinical Associate Professor, Department of Orthopaedics and Traumatology, the Chinese University of Hong Kong, and Dr Sabarul Mokhtar, Senior Consultant Orthopaedic Surgeon of the Hospital Canselor Tuanku Muhriz, Malaysia, discussed how integrating vertebral fracture assessment (VFA) into the fracture liaison service (FLS) could potentially improve vertebral fracture (VF) detection and enable early treatment of very-high-risk patients, permitting timely sequential therapy (eg, beginning with an anabolic agent and followed with a potent antiresorptive agent) to reduce imminent fracture risk, prevent subsequent hip fractures and improve outcomes.
FLS: Closing the care gap to prevent imminent fractures
A meta-analysis of global data found that the incidence of an imminent fracture after an initial fragility fracture was 7.58 percent in the first year and 11.58 percent within 2 years, with half of all refractures occurring during that period. A local study also reported that approximately 50 percent of secondary fractures happened within 2 years of the index major fragility fracture. [Osteoporos Int 2022;33:2453- 2466; Arch Osteoporos 2019;14:104] “The first 2 years therefore represent a window of opportunity to reduce imminent fracture risk within the FLS pathway,” highlighted Wong.
“With the establishment of FLS in hospitals, the service can actively identify patients with fragility fractures, assess bone health, initiate treatment and refer for rehabilitation, aiming to prevent secondary fractures, reduce hospital admissions and save medical costs,” Wong added. [Hong Kong Med J 2019;25:235-242]
“In Malaysia, the proportion of patients receiving antiosteoporosis medications after a fragility fracture has risen from 19 to 80 percent in the 5 years since FLS implementation,” noted Mokhtar. “The success of FLS depends on multidisciplinary collaboration among geriatricians, endocrinologists, obstetricians and gynaecologists, primary care physicians, and orthopaedic surgeons. Fracture cases need to be proactively identified, paying particular attention to VF detection, after which we rely on pharmacists and FLS nurses to coordinate care and optimize pre- and postoperative management. Ongoing efforts are made to adapt to local resource constraints, improve radiology engagement, reduce diagnostic waiting times and leverage new technologies to enhance patient care. Importantly, FLS nurses are the cornerstone of success as they coordinate team members and educate patients to improve adherence and disease awareness.”
VFs: Implications for risk stratification and prevention
Several clinical guidelines emphasize risk stratification and classify recent fragility fractures, including VFs, as very high risk. [Hong Kong Med J 2024:30(Suppl 2):1-44; Endocr Pract 2020;26:1-46; Osteoporos Int 2020;31:1-12] “This is very relevant for orthopaedic surgeons, as they are one of the first to encounter patients with fragility fractures,” said Wong. “It is essential to initiate secondary prevention measures early and also not to miss the window of opportunity in the first 2 years.”
“VFs are frequently underdiagnosed and undertreated because they are often clinically silent. Many patients with hip fractures have concomitant, previously undetected VFs that may occur without a fall, placing them in the very-high-risk category for future VFs and non-VFs and for increased morbidity and mortality,” emphasized Mokhtar. “Therefore, early identification and treatment of VFs may potentially prevent subsequent hip fractures.” [Am J Med 2016;129:221.e1-10; Osteoporos Int 2021;32:399-411; Osteoporos Int 2020;31:1-12]
Challenges in detecting VFs
“Back pain is frequently dismissed as ageing, and there are no universal proactive triggers. Plain radiographs can miss these fractures, dual X-ray absorptiometry [DXA] access is limited in some settings, and BMD by DXA has recognized limitations for identifying vertebral fragility,” Mokhtar highlighted.
The International Osteoporosis Foundation (IOF) recommends incorporating VFA into FLS to improve case finding and guide treatment. [Osteoporos Int 2021;32:399-411]
Proactive VF screening: Incorporating VFA into the FLS pathway
VFA is available as an option on many modern DXA machines. Performing VFA during routine BMD measurement of the lumbar spine and hips can help detect prevalent VFs in patients with recent fragility fractures attending the FLS. Evidence shows good correlation between DXA-VFA and conventional spinal radiography, with reasonably high sensitivity and specificity, although performance can vary by DXA scanner model. [Osteoporos Int 2021;32:399-411]
“As performing VFA may require additional manpower, collaboration with radiology is often necessary,” Mokhtar noted. “In hospitals without DXA-VFA, lateral thoracic and lumbar spine radiographs remain a suitable alternative.”
Interim unpublished data from local investigator‑initiated research illustrate the clinical impact of VFA. In 226 patients aged ≥60 years who underwent hip fracture surgery and concurrent DXA-VFA, around 95 percent had a concomitant VF, meaning most have ≥2 fractures. “Patients with a recent major osteoporotic fracture and a history of ≥1 previous fracture, of which ≥1 was vertebral or hip, may qualify for reimbursement of more potent antiosteoporotic agents such as an anabolic,” noted Wong. “Screening in the FLS with VFA can therefore have direct treatment implications.”
“Include self-report as a screening trigger. Ask patients, or carers, about any prior diagnosis, past imaging reports, an episode of acute severe back pain after minor trauma, or marked height loss. Refer older patients with clinical or radiological suspicion for VFA, such as women aged ≥60 years [or ≥50 years with risk factors], and men aged ≥65 years who have new height loss with or without back pain [>2 cm/year or >4 cm lifetime], a stooping posture, radiological flags on prior CT, MRI or X‑rays, such as vertebral height loss or wedge deformity, chronic glucocorticoid therapy, or self-reported but undocumented prior VF. When the back pain pathway is unclear, consider VFA and confirm fractures with lateral whole‑spine X‑rays or existing cross‑sectional imaging,” Mokhtar proposed. “FLS nurses should flag and triage these priority cases.”
Indications for VFA by DXA recommended by international guidelines are summarized in the Table.
“Training and promoting referral among other clinicians can further strengthen the FLS model and improve case finding,” Mokhtar added.
Treating very-high-risk patients with sequential therapy
The IOF recommends that patients at very high risk of a secondary fragility fracture be considered for sequential therapy with an anabolic agent followed by an antiresorptive, because anabolic agents produce larger and faster gains in BMD and earlier fracture risk reduction, which can then be maintained by an antiresorptive or antiremodelling drug. [Osteoporos Int 2020;31:1-12]
Clinical evidence supports this strategy. The 24‑month DATA‑Switch study (n=94) found that postmenopausal women who switched from an anabolic agent to an antiresorptive continued to gain BMD, whereas switching from an antiresorptive to an anabolic agent resulted in progressive, transient bone loss. [Lancet 2015;386:1147-1155]
In the pivotal FRAME study (n=7,180), 12 months of romosozumab reduced new VFs by 73 percent (incidence, 0.5 vs 1.8 percent; risk ratio [RR], 0.27; 95 percent confidence interval [CI], 0.16–0.47; p<0.001) and clinical fractures by 36 percent (1.6 vs 2.5 percent; RR, 0.64; 95 percent CI, 0.46–0.89; p=0.008) vs placebo. All patients then transitioned to denosumab. By 24 months, the cumulative VF incidence in the romosozumab‑to‑denosumab group was 75 percent lower vs the placebo‑to‑denosumab group (0.6 vs 2.5 percent; RR, 0.25; 95 percent CI, 0.16–0.40; p<0.001). (Figure) Mean absolute T‑score gains with romosozumab were 0.88 at the spine and 0.32 at the hip at 12 months, and 1.11 and 0.45 at 24 months, respectively – an effect similar to about 7 years of continuous denosumab. [N Engl J Med 2016;375:1532- 1543; J Bone Miner Res 2018;33: 1219-1226]
The ARCH study (n=4,093) also demonstrated benefit: romosozumab followed by alendronate reduced new VFs by 48 percent over 24 months (6.2 vs 11.9 percent; p<0.001) and clinical fractures by 27 percent (9.7 vs 13.0 percent; p<0.001) vs alendronate alone. [N Engl J Med 2017;377:1417-1427]
“Once a VF is confirmed and malignancy is excluded, initiate sequential therapy and provide pain management for symptomatic patients. Follow up at 3, 6, 12 and 24 months,” Mokhtar advised.
Conclusion
The high prevalence of VF makes screening essential. Incorporating VFA into the FLS facilitates detection of previously undiagnosed VFs, and often renders patients eligible for more potent treatments, including anabolic agents, which may help prevent subsequent hip fractures.
Sequential therapy, beginning with an anabolic agent and followed by a potent antiresorptive, should be considered for very‑high‑risk patients to maximize BMD gains and reduce imminent fracture risk, particularly within the first 2 years after an index fracture. Multidisciplinary FLS pathways, supported and coordinated by FLS nurses, are key to closing the osteoporosis care gap.
This special report is supported by an education grant from the industry.
