A local case sharing: Treating severe osteoporotic patients with dual-actionromosozumab
Osteoporosis per se is not a serious medical condition. Yet, it is the occurrence of fragility fractures in osteoporotic patients that makes osteoporosis a harmful disease. Among all types of osteoporotic fractures, vertebral fracture (VF)is by far the most prevalent, which could lead to immobility, loss of daily functioning and social isolation in osteoporotic patients.1,2 Despite the catastrophic consequences, VF remains seriously underdiagnosed with three-quarters of patients not seeking medical attention.1 Recognition of VF and appropriate treatment at early stage is crucial to reducing future fracture risk, as well as preventing patients’ pain, deformity, and suffering.1 In a recent interview with Omnihealth Practice, Dr. Wong, Sze-Hung discussed the looming threat of VF in Hong Kong and shared a clinical case to demonstrate the effectiveness of romosozumab, a novel anti-osteoporotic treatment option with a dual effect, in postmenopausal women with severe osteoporosis.
VF: A looming threat in Hong Kong
Due to the rapidly aging population in Hong Kong, the prevalence of osteoporosis and its associated VF has been on the rise.3 Since VF patients often present with mild symptoms such as back pain which could be resolved in a few days, they might not opt to seek medical attention, leading to a serious problem of underdiagnosis of VF.3 It was reported that only about one-third of all VF patients sought medical help.4 The issue of underdiagnosis of VF in Hong Kong could be worrying as some international studies have revealed that it was associated with substantial morbidity and increased mortality in osteoporotic patients.3,5 Many studies have already shown that the mortality risk after VF was almost as high as that after hip fractures.5 As such, a proactive approach is very much needed for making an early diagnosis of VF. Also, the adoption of appropriate pharmacological agents for treating osteoporosis and preventing the occurrence or recurrence of VF is equally important.
The need for effective anti-osteoporotic agents with dual effect
Currently in Hong Kong, bisphosphonates, as the antiresorptive drugs are among the first-line drugs and the most commonly prescribed medications for osteoporosis treatment.5 However, poor patient adherence to bisphosphonates regimen has been a long-standing issue.5 A systematic review found that many patients did not comply with the prescribed treatment of oral bisphosphonates, resulting in a substantial increase in fracture risk compared with compliant patients.5
Denosumab is another first-line antiresorptive agent that is commonly used in Hong Kong with an advantage of higher patient adherence, which was reported in the Denosumab Adherence Preference Satisfaction study in which denosumab, administered every 6 months, achieved a much higher patient adherence compared with alendronate at 2 years (92.5% vs. 63.5%).4,5 However, being an antiresorptive agent, denosumab does not increase bone strength and stimulate bone formation, which are vital for patients with severe or established osteoporosis.6
Before 2020, teriparatide (PTH) was the only anabolic or bone-forming agent available in Hong Kong for the treatment of patients with severe or established osteoporosis.7 Similar to bisphosphonates, poorpatient compliance with the PTH treatment, which is administered subcutaneously daily, leads to suboptimal therapeutic outcomes in many osteoporotic patients.6
In July 2020, the Department of Health in Hong Kong approved the use of romosozumab, a novel anti-osteoporotic agent with both bone-forming and antiresorptive effects via the inhibition of sclerostin, for the treatment of severe osteoporosis in postmenopausal women with high fracture risk.7 Owing to romosozumab’s rapid onset of action and once-monthly regimen which can bring extra convenience to patients, local clinicians generally welcome the advent of this novel alternative. Having the experience of adopting this new treatment option, Dr. Wong shared a clinical case to demonstrate its real-world effectiveness.
A 72-year-old lady with kyphosis, who had no comorbidities and had an active lifestyle, sought medical attention due to back pain. She was very thin and belonged to the classic type of older women with osteoporosis. The initial X-ray examination showed a collapse at T11 vertebra, indicating a vertebral compression fracture (VCF). Dual-energy X-ray absorptiometry (DEXA) scan was also performed and found that her T-score was -4. Given that the patient had a T-score <-2.5 and a history of fragility fracture, she was diagnosed with severe osteoporosis. Since the patient did not have a history of cardiovascular diseases and valued treatment convenience with fast response, she was then initiated with monthly romosozumab for 1 year.
After 3 months of romosozumab therapy, the patient reported a complete relief of her back pain problem. DEXA scan was conducted again at month 6, which showed a remarkable improvement in her T-score from -4 to -2.7. During the first 6 months of treatment, the patient had good adherence to the therapy and was satisfied with the treatment outcome, owing to the tremendous improvement in the T-score and the relief of her VCF symptoms. The patient did not experience any adverse events (AEs) and the treatment is still ongoing.
The clinical efficacy of romosozumab was demonstrated by a large, randomized trial named the FRAME study, in which 7,180 postmenopausal women with osteoporosis were recruited.8 After12 months of treatment, the romosozumab group (n=3,321) increased the bone mineral density (BMD) of the lumbar spine by 13.3% in these patients (95% CI: 11.9-14.7) and achieved a significant relative risk reduction (RRR) of new VFs by 73% compared with the placebo group (p<0.001).8 Some 5,743 of the recruited women continued the anti-osteoporotic treatment with denosumab every 6 months for an additional 24 months.9 After completing the treatment course, the RRR of new VFs for those treated with 12-month romosozumab (n=2,851)was maintained (66%; p<0.001) (figure 1).9 The BMD continued to rise during the 24-month denosumab therapy from 13.3% to 18.1%(p<0.001) (figure 2).9
Based on the promising findings from clinical trials, the latest Endocrine Society guidelines for the pharmacological management of osteoporosis recommend romosozumab as one of the first-line therapies for patients with severe osteoporosis and high fracture risk.10 It is also recommended to be used in patients who have failed antiresorptive treatments.10
To demonstrate the real-world effectiveness of romosozumab, a prospective cohort study was conducted.11 230 osteoporosis patients, including those who switched from another osteoporosis regimen, were recruited and prescribed with romosozumab.11The changes in BMD of the lumbar spine by DEXA scan and serum-corrected calcium level after 12 months of treatment were measured.11 The BMD increase was found to be 12.2%(p<0.001, vs. baseline), similar to the result of the clinical trial(i.e., 13.3%).11 The serum-corrected calcium level was reduced by 3.7%.11 Ever since romosozumab has become commercially available in Hong Kong, Dr. Wong utilized this novel medication in a number of osteoporotic patients and was impressed by its effectiveness. Most of his patients, including this 72-year-old lady, were able to increase their T-scores by at least 1. Some patients’ T-scores even rose by 2. Apart from the BMD benefits, romosozumab was also very effective in improving patients’ back pain problems. As shown by the FRAME extension study, continuation of anti-osteoporotic treatment with 2 additional years of denosumab therapy was effective to consolidate the BMD gain from the 1-year romosozumab treatment and maintain the RRR. As such, Dr. Wong planned to start denosumab treatment after completing the romosozumab treatment course for this patient. According to his clinical experiences, the change of treatment regimen from once monthly to every 6 months is very much welcomed by patients.
Dr. Wong recalled that in the past it was rather difficult to convince patients to initiate anti-osteoporotic treatment solely based on the DEXA scans. Nowadays, the society has become more aware of osteoporosis, making it easier for clinicians to manage the disease better. Nevertheless, the most commonly prescribed anti-osteoporotic drug in Hong Kong is still bisphosphonates, which fail to have a significant increase in BMD even after many years of treatment. In addition, bisphosphonates have been reported to be associated with a number of gastrointestinal AEs. “Although public awareness of osteoporosis has increased, people still don’t know there exists such a potent drug with a good safety profile which could increase BMD significantly in just 1 year,” Dr. Wong stated. Romosozumab has now been recommended by various international guidelines for treating postmenopausal women with severe osteoporosis, except for those with myocardial infarction or strokes within a year. However, for patients who have well-controlled hypertension or type 2 diabetes mellitus, romosozumab can still be a suitable treatment option.
Conclusion and messages to clinicians
The occurrence of fragility fractures can be extremely detrimental to patients’ quality of life and may even increase the risk of death. Prevention of fractures with appropriate pharmacological treatment is vital. Compared with the conventional therapies, romosozumab possesses the advantages of rapid onset of action, convenient monthly dosing regimen, and a shorter overall treatment duration. Therefore, it should be recommended to patients who particularly need quick treatment response and value convenience. More importantly, clinicians in Hong Kong should be more open to adopting bone-forming agents, especially romosozumab, in their osteoporotic patients, and ensure that a good treatment sequence (i.e., taking bone-forming drug followed by an antiresorptive agent) is in place. It is anticipated that with greater utilization of this novel dual-action medication, the looming threat of osteoporosis and its associated fragility fractures in the city can be contained.
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