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. 2025 Nov 19;15:40676. doi: 10.1038/s41598-025-19835-5

Analysis of the efficacy and safety of denosumab in the treatment of patients with osteoporotic vertebral compression fractures after PVP

Yixuan Jiang 1, Bowen He 2, Qi Shang 3,4, Hao Liu 1, Wanyan Chen 1, WenHua Zhao 3,4, Gengyang Shen 3,4,✉, Hui Ren 3,4, Xiaobing Jiang 3,4,✉
PMCID: PMC12630939  PMID: 41258154

Abstract

The overall purpose of this study was to explore the efficacy of denosumab in the treatment of osteoporotic vertebral fractures and to compare the efficacy of denosumab in osteoporotic vertebral compression fracture (OVCF) patients with or without a history of osteoporotic fractures. We included 70 patients with single-segment OVCFs who underwent percutaneous vertebral plasty (PVP) at our hospital between October 2020 and April 2022. All postoperative patients received one year of anti-osteoporosis treatment, adopting conventional basic treatment methods such as oral calcium and vitamin D supplements, with subcutaneous injections of denosumab at 60 mg/time every six months (for a total of two times). Patients were grouped on the basis of whether they had previously experienced osteoporotic fractures, and changes in bone mineral density (BMD) of the lumbar spine and hip before and one year after treatment were recorded. Additionally, changes in the preoperative visual analogue scale (VAS) score for back pain and the Oswestry Disability Index (ODI) were observed, as were adverse drug reaction and recurrent fracture incidences. Anterior and posterior vertebral height and sagittal Cobb angle changes were measured on anteroposterior and lateral X-ray films before and after treatment. The results revealed that one year after denosumab treatment, the BMD values at all sites were significantly greater in the 70 patients than before treatment (P < 0.05). Both the group with a history of osteoporotic fractures and the group without a history of osteoporotic fractures (predominantly OVCFs) showed improvements in BMD at various sites. Furthermore, compared with a history of osteoporotic fractures, denosumab was more effective at improving the BMD of patients with their first osteoporotic fracture.

Subject terms: Clinical trial design, Fracture repair, Prognosis

Introduction

Osteoporosis is a systemic disease characterized by decreased bone mass and destruction of the bone tissue microstructure, leading to increased bone fragility and susceptibility to fractures1. Among these, the most severe consequence is the occurrence of osteoporotic fractures triggered by increased bone fragility. Osteoporotic fractures most commonly occur in thoracolumbar vertebral bodies2. Osteoporosis is commonly observed in postmenopausal women and elderly men but can also occur at any age3. China has an ageing society. According to the results of the 7th National Population Census in 2020, the population aged 60 and above reached 264.02 million, accounting for 13.5% of the total population. The population of women aged 50 years and above in China has reached 230 million, with an osteoporosis prevalence rate of up to 32.1% in this age group. Therefore, osteoporosis has become an important public health issue in China3. Owing to decreased oestrogen levels in postmenopausal women, receptor activator of nuclear factor-κB (RANKL) expression increases, osteoprotegerin (OPG) levels decrease, and the RANKL/OPG ratio increases, resulting in weakened osteoclast inhibition. This leads to enhanced osteoclast differentiation and activity, increased number, reduced apoptosis, enhanced bone resorption, disrupted bone remodelling balance, accelerated bone loss, and increased incidence of osteoporosis3.

Denosumab is a humanized monoclonal antibody against RANKL4 and is currently the most potent RANKL inhibitor used in human treatment. It binds to RANKL with high affinity, thereby inhibiting the interaction between RANKL and RANK and suppressing the formation and function of osteoclasts. Denosumab reduces bone resorption, increases bone mass, improves bone strength, and lowers the risk of fractures5. Denosumab binds to RANKL with high specificity, and no binding has been observed with other members of the TNF family, such as TNFα and TNFβ6. Denosumab is currently the only marketed RANKL inhibitor that was first approved in the EU in 2010 for the treatment of postmenopausal women and men with osteoporosis at high risk of fracture. According to foreign studies, denosumab has been demonstrated to significantly reduce the risk of hip, vertebral, and nonvertebral fractures in postmenopausal women7. The drug was approved for marketing in China in June 2020. Currently, there are relatively few reports on the efficacy of denosumab in treating osteoporotic vertebral fractures, and there are even fewer reports on the efficacy of denosumab in treating OVCF patients with a history of osteoporotic vertebral fractures. The primary objective of this study was to retrospectively analyse the efficacy and safety of denosumab in patients with OVCFs after percutaneous vertebroplasty (PVP). Although zoledronic acid (ZOL) also inhibits bone resorption, denosumab and ZOL have different therapeutic effects in the treatment of Skeletal Related Events (SRES)8. Although these two drugs have comparable effects in improving overall survival and delaying disease progression, denosumab has shown greater efficacy in reducing specific SREs, such as bone radiotherapy for breast cancer and pathological fractures, and prolongs the interval without SRE in most cancers8. In addition, for postmenopausal women with osteoporosis, denosumab has a better effect than zoledronic acid on improving bone mineral density, trabecular bone score and inhibiting bone remodelling in two-year treatment, and its persistence is higher9. Despite its high cost, denosumab’s good safety (including fewer renal events and acute phase reactions), as well as its convenience and ability to delay pain progression, provide clinical advantages. Previous studies have fully verified the effect of ZOL, while this study aims to explore the new evidence of denosumab.

Materials and methods

Patients

We selected 70 patients with single-segment OVCFs admitted to our hospital between October 2020 and April 2021, with an average age of 72.43 ± 9.70 years, height of 154.20 ± 7.18 cm, weight of 53.27 (35.00, 83.00) kg, and body mass index (BMI) of 22.34 (17.00, 35.00) kg/m2. The duration of illness ranged from 1.0 to 4.0 months, with an average of 1.8 months. Among them, 31 patients had no obvious history of trauma, and 39 patients had a history of falls (low-energy injuries). Fracture vertebral body distribution: 17 cases in the thoracic vertebrae (T1-9), 44 cases in the thoracolumbar vertebrae (T10-L2), and 9 cases in the lumbar vertebrae (L3-L5). The specific details are shown in Table 1.

Table 1.

Patient demographics (n = 70).

Characteristics Value
Age (years) 72.43 ± 9.70
Height (cm) 154.20 ± 7.18
Weight (kg) 51.50 (45.00, 60.00)
BMI (g/m2) 22.00 (19.00, 24.00)
Fracture site
Thoracic vertebra (T1–9) 17
Thoracolumbar vertebra (T10–L2) 44
Lumbar vertebra (L3–L5) 9
Damage type
No obvious history trauma 31
Low energy damage 39
History of osteoporotic fractures
Yes 40
Average number of previous fractures 1.25
No 30
Current smoker
Yes 66
NO 4
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Inclusion criteria

(1) Patients definitively diagnosed with single-level fresh OVCFs based on CT and MR imaging examinations; (2) Patients who have undergone nonsurgical treatment for 4 to 6 weeks with poor or ineffective results or whose X-ray images show progressive aggravation of kyphosis deformity; (3) Patients who agreed to undergo percutaneous vertebroplasty (PVP) treatment and signed a surgical informed consent form; (4) Patients who receive routine basic treatment methods such as oral calcium and vitamin D supplements after surgery and receive subcutaneous injections of denosumab (60 mg/time, twice in total) every six months.

Exclusion criteria

1.Patients with hypocalcaemia; 2. Patients with impaired immune function or those who had recently taken immunosuppressants; 3. Patients with neoplastic diseases; 4. Patients with drug allergies.

Surgical treatment

All patients with a definitive diagnosis of single-segment osteoporotic fractures underwent PVP under local anaesthesia after signing the surgical informed consent form. Technical improvements have been made in traditional PVP, including two key techniques: fracture area puncture catheterization and side-port plunger injection of bone cement. The specific steps are detailed in reference10.

Anti-osteoporosis drug treatment

Calcium and vitamin D3 were administered orally daily. Denosumab, produced by Amgen Inc., USA, was used at 60 mg/vial. Patients received a subcutaneous abdominal injection of denosumab at 60 mg/time every six months (two injections within one year). All postoperative patients received one year of treatment. BMD and bone marker-related indicators of the lumbar spine and hip, as well as VAS pain score changes, were recorded before and one year after treatment. Drug adverse reactions, fracture healing of the injured vertebra, and recurrent fracture incidence were observed.

Observation indicators

(1) Changes in BMD before and after treatment were measured using the GE Prodigy dual-energy X-ray absorptiometry (DXA) system to assess BMD values at the lumbar spine (L1-4), left hip, and left femoral neck (for lumbar spine fracture patients (L1-4)), and the average BMD value of the remaining lumbar spine was measured postoperatively. Analysis of BMD changes before and one year after treatment; (2) The clinical efficacy before and after treatment was evaluated. The visual analogue scale (VAS) was used to assess the level of pain in patients, with scores ranging from 0 to 10, with higher scores indicating more severe pain. The VAS pain scoring criteria are as follows: 0 points indicates no pain; less than 3 points indicates mild pain that the patient can tolerate; 4 to 6 points indicate that the patient experiences pain and impaired sleep but can still tolerate it; and 7 to 10 points indicate that the patient experiences extremely intense pain that is unbearable. Moreover, when the ODI functional impairment index score was used, the higher the score was, the greater the degree of functional impairment. The ODI score covers three major areas of assessment: pain (severity of pain, impact of pain on sleep), individual functions (lifting, sitting, standing, walking), and comprehensive personal functions (daily activity ability, sexual activity, social activities, and outings). Changes in the anterior vertebral body height, lowest vertebral body height, posterior vertebral body height, and Cobb angle in the sagittal plane before and after treatment were observed. Fracture healing, the incidence of refracture, and adverse reactions after 1 year of treatment were observed. Adverse drug reactions include fever, nausea and vomiting, muscle pain, etc.

Results

Comparison of bone mineral density (BMD) before and after treatment

The BMD values at various sites one year after treatment were significantly greater than those before treatment (P < 0.05), as shown in Table 2. LV-BMD indicates the lumbar vertebral BMD, HJ-BMD indicates the hip joint BMD, and NOF-BMD indicates the neck femoral BMD.

Table 2.

Changes in BMD values at various sites before and after treatment (n = 70), “t” refers to the t-statistic used in the t-test, which is derived from student’s t-distribution.

LV-BMD (g/cm2) HJ-BMD (g/cm2) NOF-BMD (g/cm2)
Before 0.716 ± 0.14 0.630 ± 0.11 0.670 ± 0.12
After1 year 0.750 ± 0.13 0.656 ± 0.11 0.690 ± 0.12
t 4.54 3.02 3.36
P <0.001 <0.05 <0.05
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The 70 patients with OVCFs were grouped on the basis of whether they had previously experienced osteoporotic fractures. In the group without previous osteoporotic fractures, the LV-BMD before treatment was 0.738 ± 0.15 g/cm2 and increased to 0.765 ± 0.15 g/cm2 after treatment. The HJ-BMD before treatment was 0.620 ± 0.09 g/cm2 and increased to 0.662 ± 0.09 g/cm2 after treatment. The NOF-BMD before treatment was 0.674 ± 0.11 g/cm2 and increased to 0.716 (0.56, 0.80) g/cm2 after treatment. Compared with those before treatment, the BMD values at all sites improved after treatment, and the improvements were statistically significant (P < 0.05). In the group with previous osteoporotic fractures, the LV-BMD before treatment was 0.699 ± 0.12 g/cm2 and increased to 0.739 ± 0.12 g/cm2 after treatment. The HJ-BMD before treatment was 0.637 ± 0.12 g/cm2 and increased to 0.651 ± 0.11 g/cm2 after treatment. The NOF-BMD before treatment was 0.667 ± 0.13 g/cm2 and increased to 0.682 ± 0.13 g/cm2 after treatment. Compared with those before treatment, the BMD values at all sites improved after treatment, but only the improvement in the LV-BMD was statistically significant. The improvements in HJ-BMD and NOF-BMD were not statistically significant (P > 0.05), as shown in Fig. 1.

Fig. 1.

Fig. 1

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Changes in BMD at various sites before and one year after denosumab treatment. (A) The BMD values at all sites improved after treatment compared with before treatment, and the improvements were statistically significant (all P < 0.05). (B) In the group without previous osteoporotic fractures, the BMD values at all sites improved after treatment compared with before, and the improvements were statistically significant (all P < 0.05). (C) In the group with previous osteoporotic fractures, the BMD values at all sites improved after treatment compared with before treatment, but only the improvement in the LV-BMD was statistically significant (P < 0.05). OVCF (-) refers to the group that has not experienced osteoporotic fractures in the past. OVCF (+) refers to the group that previously experienced osteoporotic fractures. Except for the NOF-BMD-OVCF (-) group, for which the Wilcoxon test was used, all other groups were subjected to paired t tests.

There was a statistically significant difference in the change in HJ-BMD before and after treatment between the group without previous osteoporotic fractures and the group with previous osteoporotic fractures (P < 0.05). There were no statistically significant differences in the changes in the LV-BMD or NOF-BMD between the two groups (P > 0.05), as shown in Fig. 2.

Fig. 2.

Fig. 2

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Differences in BMD changes before and after treatment between groups with and without previous osteoporotic fractures. (A) Differences in LV-BMD changes before and after treatment between the two groups. (B) Differences in HJ-BMD changes before and after treatment between the two groups. (C) Differences in NOF-BMD changes before and after treatment between the two groups. Only the difference in HJ-BMD changes between the two groups was statistically significant (P < 0.05). OVCF (-) refers to the group that has not experienced osteoporotic fractures in the past. OVCF (+) refers to the group that previously experienced osteoporotic fractures. Each set of data was analysed using the Mann–Whitney test.

Comparison of the VAS and ODI scores as indicators of efficacy

The VAS pain index and ODI disability index scores of the 70 patients decreased after treatment compared with before treatment, and the differences were statistically significant (P < 0.001), as shown in Table 3.

Table 3.

Comparison of VAS and ODI scores before and after treatment (n = 70).

Time VAS ODI
Before 7.00 (7.00, 8.00) 0.89 (0.87, 0.96)
After 3 days 2.00 (2.00, 3.00) ** 0.42 (0.32, 0.49)**
After 1 year 1.00 (1.00, 2.00) ** 0.23 (0.21, 0.28)**
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Compared with before treatment using the Wilcoxon signed-rank test, *P < 0.05, **P < 0.001.

The 70 patients with OVCFs were grouped on the basis of whether they had previously experienced osteoporotic fractures. The VAS score before treatment in the group without previous osteoporotic fractures was 7.00 (7.00, 8.00), which decreased to 2.50 (2.00, 3.00) three days after surgery and 1.00 (1.00, 2.00) one year after surgery. There were statistically significant differences compared with before treatment (P < 0.001). In the group with previous osteoporotic fractures, the score before treatment was 7.00 (7.00, 8.00), which decreased to 2.00 (2.00, 3.00) three days after surgery and 1.50 (1.00, 2.00) one year after surgery. Statistically significant differences were noted compared with before treatment (P < 0.001), as shown in Fig. 3.

Fig. 3.

Fig. 3

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Changes in VAS scores before and one year after denosumab Treatment. (A) Compared with those before surgery, the VAS scores of all patients improved three days and one year after surgery, and the improvements were statistically significant (both P < 0.001). (B) In the group without previous osteoporotic fractures, the VAS score improved significantly three days and one year after surgery compared with before surgery (both P < 0.001). (C) In the group with previous osteoporotic fractures, the VAS score improved significantly three days and one year after surgery compared with before surgery (both P < 0.001). OVCF (-) refers to the group that has not experienced osteoporotic fractures in the past. OVCF (+) refers to the group that previously experienced osteoporotic fractures. Each set of data was analysed using the Wilcoxon test.

The ODI score before treatment in the group without previous osteoporotic fractures was 0.89 (0.87, 0.96), which decreased to 0.42 (0.32, 0.49) three days after surgery and 0.24 (0.22, 0.29) one year after surgery. There were statistically significant differences compared with before treatment (P < 0.001). In the group with previous osteoporotic fractures, the score before treatment was 0.89 (0.87, 0.96). This value decreased to 0.41 ± 0.08 three days after surgery and 0.23 (0.21, 0.28) one year after surgery. There were statistically significant differences compared with before treatment (P < 0.001), as shown in Fig. 4.

Fig. 4.

Fig. 4

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Changes in ODI Scores Before and One Year After Denosumab Treatment. (A) Compared with those before surgery, the ODI scores of all patients improved three days and one year after surgery, and the improvements were statistically significant (both P < 0.001). (B) In the group without previous osteoporotic fractures, the ODI score improved significantly (both P < 0.001) three days and one year after surgery compared with before surgery. (C) In the group with previous osteoporotic fractures, the ODI score improved three days and one year after surgery compared with before surgery, and the improvements were statistically significant (both P < 0.001). OVCF (-) refers to the group that has not experienced osteoporotic fractures in the past. OVCF (+) refers to the group that previously experienced osteoporotic fractures. Each set of data was analysed using the Wilcoxon test.

There were no statistically significant differences in the changes in the VAS and ODI scores between the group without previous osteoporotic fractures and the group with previous osteoporotic fractures, either three days after treatment or at the final follow-up (P > 0.05), as shown in Fig. 5.

Fig. 5.

Fig. 5

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Differences in the VAS and ODI Score Changes Between the Group With and Without Previous Osteoporotic Fractures Before and After Treatment. (A) There were no statistically significant differences in the changes in VAS scores between the two groups, either three days after treatment or at the final follow-up (P > 0.05). (B) There were no statistically significant differences in the changes in the ODI scores between the two groups, either three days after treatment or at the final follow-up (P > 0.05). OVCF (-) refers to the group that has not experienced osteoporotic fractures in the past. OVCF (+) refers to the group that previously experienced osteoporotic fractures. The data in Group A were analysed using the Mann–Whitney test. The data in Group B were analysed using unpaired t tests.

Changes in the height of injured vertebrae and the sagittal Cobb angle before and after treatment

Seventy patients underwent PVP (percutaneous vertebroplasty) and denosumab antiosteoporosis treatment for one year. The changes in the anterior vertebral height, minimum vertebral height, posterior vertebral height, and sagittal Cobb angle before and after treatment were statistically significant (P < 0.05). See Table 4 for details.

Table 4.

Changes in the height of injured vertebrae and the sagittal Cobb angle before and after treatment (n = 70).

Time AH (mm) Minimum height (mm) PH (mm) Cobb angle (°)
Before 17.60 ± 5.22 13.39 ± 4.40 21.26 ± 5.14 6.78 (3.00, 11.26)
After 3 days 20.69 ± 4.61 ** 17.14 ± 4.76 ** 22.91 ± 4.82 ** 4.92 (1.61, 7.39)**
After 1 year 20.30 ± 5.07 ** 16.90 ± 5.16 ** 22.00 ± 5.22 3.30 (2.01, 5.71)**
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Adverse reactions and recurrent fracture incidence

None of the 70 patients experienced acute adverse reactions such as fever, nausea and vomiting, muscle pain, or allergies. Among them, two patients experienced skeletal muscle pain. No cases of rare hypocalcaemia, hypersensitivity reactions, osteonecrosis of the jawbone, or atypical femoral fractures were observed. Follow-up within one year revealed no nonhealing of the injured vertebrae, and three cases of recurrent vertebral fractures occurred. Among them, two patients accidentally fell, and one patient developed low back pain without obvious inducement and was diagnosed with osteoporotic vertebral fracture at the hospital. The incidence of recurrent fracture was 3.85%. See Table 5 for details.

Table 5.

Number of adverse reactions or recurrent fractures (n = 70).

Adverse reaction Value
Acute adverse reaction 0
Hypocalcaemia 0
Hypersensitivity reactions 0
Osteonecrosis of the jawbone 0
Atypical femoral fractures 0
Skeletal muscle pain 2
Nonhealing 1
Recurrent vertebral fracture 3
Accidentally falling 2
No obvious cause 1
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Discussion

Osteoporosis is a metabolic bone disease characterized by reduced bone mass and disruption of bone microarchitecture. Osteoporosis is associated with an increased risk of bone fragility and contributes to significant morbidity and mortality11. Fractures represent the most severe consequence of osteoporosis, with high rates of disability and mortality, and pose a substantial burden on families and society. The World Health Organization has identified osteoporosis as one of the ten most serious diseases globally. With the continuous growth of the global population and the ageing trend, the incidence of OVCFs has been increasing annually, affecting more than 1.4 million people worldwide each year and becoming a nonnegligible issue for elderly individuals12. Clinically, percutaneous vertebroplasty (PVP) is one of the main surgical treatments for OVCFs, and targeted PVP can enable more adequate bone cement dispersion, better stabilize the fracture area, provide rapid pain relief, and promote patient recovery, as shown in Fig. 6.

Fig. 6.

Fig. 6

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A classic case of PVP. Conventional vertebroplasty can easily lead to poor dispersion in the fracture area, so targeted vertebroplasty was adopted here. A side-opening pusher was used to puncture the pusher to the lower part of the fracture area, controlling the direction of the bone cement injection. Bone cement was injected into the nonfracture area below until bone cement anchoring formed in the nonfracture area. Then, the opening of the pusher was adjusted in a targeted manner towards the fracture area, allowing the bone cement to fully disperse within the fracture area.

Following PVP, patients are generally advised to undergo active anti-osteoporosis treatment. Among them, calcium serves as the foundational element of anti-osteoporosis therapy, whereas vitamin D plays a role in promoting calcium absorption during anti-osteoporosis treatment, functioning as a tool and medium. Together, they work towards combating osteoporosis. Additionally, patients need to adjust their lifestyles, use essential supplements beneficial to bone health, engage in regular exercise, ensure adequate sunlight exposure, quit smoking, limit alcohol consumption, avoid beverages that can cause calcium loss, and reduce the use of medications that affect bone markers. However, there are drawbacks, particularly the significantly increased risk of rebound vertebral fractures after the discontinuation of denosumab in patients following PVP surgery, especially in elderly patients with low bone density and a history of fracture. Clinical practice should emphasize the importance of long-term standardized medication and reduce risks through multidisciplinary management13–19 (pharmacotherapy, nutrition, and rehabilitation). If discontinuation is necessary, individualized sequential treatment plans should be developed to prevent a cliff-like increase in fracture risk.

The findings of this study revealed that one year after denosumab treatment, the bone mineral density (BMD) values at various sites were significantly greater in 70 patients than they were before treatment (P < 0.05). Both the group with a history of osteoporotic fractures and the group without a history of fractures (primarily with osteoporotic vertebral fractures) showed improvements in BMD at various sites. Furthermore, compared with a history of osteoporotic fractures, denosumab demonstrated better efficacy in improving BMD in patients with a first-time osteoporotic fracture. These findings suggest that denosumab can sustainably increase BMD in patients after osteoporotic vertebral fracture surgery, which may be related to strong bone resorption in patients with osteoporosis and fragility fractures. Denosumab inhibits the interaction between RANKL and RANK, thereby inhibiting the formation and function of osteoclasts and ultimately increasing bone mass and improving bone strength. After treatment, the VAS pain index and ODI scores of the 70 patients improved, with statistically significant differences before and after treatment (P < 0.001). This study also compared the VAS and ODI scores before and after denosumab use in patients with and without a history of osteoporotic vertebral fractures. The results suggested that denosumab could help improve low back pain symptoms and quality of life in patients after osteoporotic vertebral fracture surgery, regardless of their history of such fractures, thereby reducing the disability rate. This is consistent with the findings reported by Kwon et al.20. It is associated with adequate bone cement dispersion in the fracture area after targeted PVP, enhancing fracture stability. The inhibition of osteoclast activity by denosumab and the reduction in the inflammatory cytokine response21–23 are also contributing factors to the improvement of clinical symptoms in patients. After targeted PVP and denosumab treatment, the changes in anterior vertebral height, minimum vertebral height, posterior vertebral height, and the sagittal Cobb angle were statistically significant when compared before treatment, after postoperative follow-up, and at the final follow-up (P < 0.05). Postoperative and final follow-up assessments revealed improvements in injured vertebral height and kyphosis compared with preoperative assessments. Effective reduction was achieved, and no nonunion of injured vertebrae was observed in the radiological follow-up of 70 patients within one year. This observation is similar to the findings of Hegde V, who reported that denosumab does not affect fracture healing in animal experiments24.

In the context of China’s ageing population and the increasing prevalence of osteoporosis, the six-month subcutaneous injection dosing regimen of denosumab significantly improved patient compliance and satisfaction25. In terms of short-term efficacy, denosumab has a lower rate of acute adverse reactions, such as fever, than ZOL, which is a first-line drug for osteoporosis (OP). Black et al.26 reported that transient fever, myalgia, and other acute-phase reactions commonly occur after the first intravenous infusion of ZOL, with incidences of approximately 15% for fever, 5% for joint pain, 8% for muscle pain, and 7% for headache. These acute-phase reactions are mostly mild to moderate, occurring within 3 days after infusion and resolving within the same timeframe without serious complications27. Denosumab is easier to administer, effectively reducing the workload of medical staff and the burden on patients seeking medical treatment. A study by Lan et al.28 indicated that the renal toxicity induced by ZOL may be due to its disruption of glutathione biosynthesis and the tricarboxylic acid cycle, leading to excessive generation of reactive oxygen species, oxidative stress, and cellular inflammation, ultimately causing renal toxicity. Intravenous infusion of ZOL can cause significant renal toxicity associated with acute tubular necrosis and renal fibrosis. However, in a study involving patients with varying degrees of renal impairment (including those undergoing dialysis), the degree of renal impairment had no effect on the pharmacokinetics of denosumab. Currently, no specific studies have been conducted on the pharmacokinetics of denosumab in patients with hepatic impairment. Typically, monoclonal antibodies are not metabolized and cleared by the liver, suggesting that hepatic impairment may not affect the pharmacokinetics of denosumab29. These pharmacokinetic characteristics provide a new “weapon” for the systematic and regular anti-osteoporosis treatment of patients with primary osteoporosis and impaired liver or kidney function. In the FREEDOM 3-year study, no cases of atypical femoral fractures were observed in the denosumab treatment group. At 36 months, denosumab significantly reduces the fracture risk and increases the BMD at various sites, with good safety30,31.

This study demonstrated that the clinical application of denosumab in patients after osteoporotic vertebral fracture surgery can effectively improve patients’ pain and quality of life, increase BMD, and reduce the risk of osteoporotic fractures, especially for patients with a first-time osteoporotic vertebral fracture. Denosumab is associated with few acute adverse reactions, such as fever and allergies, in the short term and is an effective and generally safe drug for the treatment of osteoporosis32. This study has certain limitations. Owing to the limited sample size and short observation period, the long-term clinical efficacy and safety of denosumab in patients after osteoporotic vertebral fracture surgery in China need further study and observation. In the future, the sample size can be expanded, and the impact of long-term use of denosumab on patients after osteoporotic vertebral fracture surgery can be studied in combination with BMD, bone markers, and fracture incidence.

Limitations

This study has limitations. Owing to the limited sample size and relatively short observation period, further research is needed to investigate the clinical efficacy and safety of long-term denosumab use in Chinese patients following osteoporotic vertebral fracture surgery. In the future, the sample size can be expanded, and the impact of long-term denosumab use on patients postosteoporotic vertebral fracture surgery can be studied in conjunction with bone mineral density (BMD), bone markers, and fracture incidence rates.

Summary

The BMD values of various anatomical sites of 70 patients significantly increased after one year of treatment with denosumab compared to before treatment, indicating that denosumab continued to increase bone density in OVCF patients after PVP surgery. Among them, the group without previous osteoporotic vertebral fractures showed improvement in bone density in all parts compared with the preoperative levels, whereas the group with previous osteoporotic fractures only showed significant improvement in LV-BMD compared with the preoperative levels. In addition, compared with patients with a history of OVCFs, denosumab improved HJ-BMD better in patients with first-time OVCFs. This may be related to strong bone resorption in most patients with osteoporosis and fragility fractures. These findings indicate that denosumab has a stronger effect on increasing bone density in patients without a history of OVCF. In terms of the VAS score and ODI score, regardless of a history of OVCF, patients’ scores significantly improved after denosumab treatment compared with before treatment, with no significant difference noted between the groups.

Author contributions

Yixuan Jiang and Bowen He conducted data analysis and wrote the manuscript; Wanyan Chen, Wenhua Zhao, and Hao Liu made significant contributions to the analysis and manuscript preparation; Qi Shang helps with analysis through constructive discussions; Gengyang Shen, Hui Ren, and Xiaobing Jiang contributed to the conception of this research. All authors have made significant scientific contributions to the research presented in the aforementioned manuscript, have approved their statements, and agree to become authors.

Funding

The fund is supported by the “Orthopedic Osteoporosis Innovation Fund” of the China Medicine Education Association ([2022]067).

Data availability

The datasets generated and analysed during the current study are not publicly available due to the protection of patient privacy but are available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The authors confirm that the study was performed in accordance with the Declaration of Helsinki.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Gengyang Shen, Email: 15920198161@163.com.

Xiaobing Jiang, Email: spinedrjxb@sina.com.

References

  • 1.Niu, P. et al. Association between HDL-C and bone mineral density: an Cross-Sectional analysis. Int. J. Gen. Med.14, 8863–8872. 10.2147/ijgm.S334972 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Chiodini, I., Falchetti, A., Merlotti, D., Eller Vainicher, C. & Gennari, L. Updates in epidemiology, pathophysiology and management strategies of glucocorticoid-induced osteoporosis. Expert Rev. Endocrinol. Metabolism. 15, 283–298. 10.1080/17446651.2020.1772051 (2020). [DOI] [PubMed] [Google Scholar]
  • 3.Cheng, C. H., Chen, L. R. & Chen, K. H. Osteoporosis due to hormone imbalance: an overview of the effects of Estrogen deficiency and glucocorticoid overuse on bone turnover. Int. J. Mol. Sci.23, 17. 10.3390/ijms23031376 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Huang, H. K. et al. Denosumab and the risk of diabetes in patients treated for osteoporosis. JAMA Netw. Open.7, 13. 10.1001/jamanetworkopen.2023.54734 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.El-Masri, B. M. et al. Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect. Bone Res.12, 21. 10.1038/s41413-024-00362-4 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Oryniak, D., Brown, M., Cholakis, L., Elgazzar, R. & Case Report Development of medication-related osteonecrosis of the jaw in a patient on long-term Infliximab therapy. Front. Oral Health. 5, 1427060. 10.3389/froh.2024.1427060 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Everts-Graber, J. et al. Comparison of anti-fracture effectiveness of zoledronate, ibandronate and alendronate versus denosumab in a registry-based cohort study. Osteoporos. Int.34, 1961–1973. 10.1007/s00198-023-06863-y (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Wajda, B. G. et al. Denosumab vs. Zoledronic acid for metastatic bone disease: A comprehensive systematic review and Meta-Analysis of randomized controlled trials. Cancers1710.3390/cancers17030388 (2025). [DOI] [PMC free article] [PubMed]
  • 9.Kang, T., Park, S. Y., Lee, S. H., Park, J. H. & Suh, S. W. Comparison of denosumab and Zoledronic acid in postmenopausal women with osteoporosis: bone mineral density (BMD) and trabecular bone score (TBS). J. Korean Med. Sci.3710.3346/jkms.2022.37.e68 (2022). [DOI] [PMC free article] [PubMed]
  • 10.Wang, X., Zhu, Y. H. & Zhu, Q. S. Efficacy and safety of robot-assisted versus fluoroscopy-assisted PKP or PVP for osteoporotic vertebral compression fractures: a systematic review and meta-analysis. J. Robot Surg.17, 2597–2610. 10.1007/s11701-023-01700-0 (2023). [DOI] [PubMed] [Google Scholar]
  • 11.Morin, S. N. et al. Clinical practice guideline for management of osteoporosis and fracture prevention in canada: 2023 update. Can. Med. Assoc. J.195, E1333–E1348. 10.1503/cmaj.221647 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Dai, C. Q., Liang, G., Zhang, Y. S., Dong, Y. & Zhou, X. D. Risk factors of vertebral re-fracture after PVP or PKP for osteoporotic vertebral compression fractures, especially in Eastern asia: a systematic review and meta-analysis. J. Orthop. Surg. Res.17, 11. 10.1186/s13018-022-03038-z (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Zou, J. et al. A Real-world study of denosumab for reducing refracture risk after percutaneous vertebral augmentation. Orthop. Surg.16, 1849–1860. 10.1111/os.14087 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Anastasilakis, A. D. et al. Similarities and differences in the management of patients with osteoporotic vertebral fractures and those with Rebound-Associated vertebral fractures following discontinuation of denosumab. J. Clin. Med.1210.3390/jcm12185874 (2023). [DOI] [PMC free article] [PubMed]
  • 15.Anastasilakis, A. D. et al. Clinical features of 24 patients with Rebound-Associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J. Bone Min. Res.32, 1291–1296. 10.1002/jbmr.3110 (2017). [DOI] [PubMed] [Google Scholar]
  • 16.Kao, F. C., Hsu, Y. C., Chen, T. S., Tu, Y. K. & Liu, P. H. Effects of injected antiosteoporotic medication versus oral bisphosphonates on rates of repeated vertebroplasty or kyphoplasty. Clin. Ther.42, 1087–1098e1082. 10.1016/j.clinthera.2020.04.011 (2020). [DOI] [PubMed] [Google Scholar]
  • 17.Tripto-Shkolnik, L., Liel, Y., Yekutiel, N. & Goldshtein, I. Long-Term Follow-Up of denosumab discontinuers with multiple vertebral fractures in the Real-World: A case series. Horm. Metab. Res.53, 185–190. 10.1055/a-1368-4218 (2021). [DOI] [PubMed] [Google Scholar]
  • 18.Dupont, J. et al. Rebound-associated vertebral fractures after stopping denosumab: report of four cases. Joint Bone Spine. 87, 171–173. 10.1016/j.jbspin.2019.07.010 (2020). [DOI] [PubMed] [Google Scholar]
  • 19.Lamy, O., Gonzalez-Rodriguez, E., Stoll, D., Hans, D. & Aubry-Rozier, B. Severe Rebound-Associated vertebral fractures after denosumab discontinuation: 9 clinical cases report. J. Clin. Endocrinol. Metab.102, 354–358. 10.1210/jc.2016-3170 (2017). [DOI] [PubMed] [Google Scholar]
  • 20.Kwon, B. T., Ham, D. W., Park, S. M., Kim, H. J. & Yeom, J. S. Impact of teriparatide and denosumab on clinical and radiographic outcomes in osteoporotic vertebral compression fractures. Med. Lith.60, 10. 10.3390/medicina60081314 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Lasschuit, J. W. J., Center, J. R., Greenfield, J. R. & Tonks, K. T. T. Effect of denosumab on inflammation and bone health in active Charcot foot: A phase II randomised controlled trial. J. Diabetes Complications. 38, 9. 10.1016/j.jdiacomp.2024.108718 (2024). [DOI] [PubMed] [Google Scholar]
  • 22.Baron, R., Ferrari, S. & Russell, R. G. G. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone48, 677–692. 10.1016/j.bone.2010.11.020 (2011). [DOI] [PubMed] [Google Scholar]
  • 23.Cai, G. Q. et al. Effect of Zoledronic acid and denosumab in patients with low back pain and modic change: A Proof-of-Principle trial. J. Bone Min. Res.33, 773–782. 10.1002/jbmr.3376 (2018). [DOI] [PubMed] [Google Scholar]
  • 24.Hegde, V., Jo, J. E., Andreopoulou, P. & Lane, J. M. Effect of osteoporosis medications on fracture healing. Osteoporos. Int.27, 861–871. 10.1007/s00198-015-3331-7 (2016). [DOI] [PubMed] [Google Scholar]
  • 25.Hofbauer, L. C. & Rauner, M. Denosumab-Protection for bone and beyond?? Clin. Endocrinol. Metab.109, e2159–e2160. 10.1210/clinem/dgae207 (2024). [DOI] [PubMed] [Google Scholar]
  • 26.Black, D. M. et al. The interaction of Acute-Phase reaction and efficacy for osteoporosis after Zoledronic acid: HORIZON pivotal fracture trial. J. Bone Min. Res.37, 21–28. 10.1002/jbmr.4434 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Lu, K. et al. The impact of acute-phase reaction on mortality and re-fracture after Zoledronic acid in hospitalized elderly osteoporotic fracture patients. Osteoporos. Int.34, 1613–1623. 10.1007/s00198-023-06803-w (2023). [DOI] [PubMed] [Google Scholar]
  • 28.Lan, Z., Chai, K., Jiang, Y. & Liu, X. Characterization of urinary biomarkers and their relevant mechanisms of zoledronate-induced nephrotoxicity using rats and HK-2 cells. Hum. Exp. Toxicol.38, 598–609. 10.1177/0960327119829527 (2019). [DOI] [PubMed] [Google Scholar]
  • 29.Zhang, S. H. et al. Efficacy, safety, and population pharmacokinetics of MW032 compared with denosumab for solid Tumor-Related bone metastases. JAMA Oncol.10, 448–455. 10.1001/jamaoncol.2023.6520 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Cummings, S. R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl. J. Med.361, 756–765. 10.1056/NEJMoa0809493 (2009). [DOI] [PubMed] [Google Scholar]
  • 31.Kendler, D. L. et al. The risk of subsequent osteoporotic fractures is decreased in subjects experiencing fracture while on denosumab: results from the FREEDOM and FREEDOM extension studies. Osteoporos. Int.30, 71–78. 10.1007/s00198-018-4687-2 (2019). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Ramchand, S. K. et al. The comparison of alendronate and raloxifene after denosumab (CARD) study: A comparative efficacy trial. Osteoporos. Int.910.1007/s00198-023-06932-2 (2023). [DOI] [PubMed]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets generated and analysed during the current study are not publicly available due to the protection of patient privacy but are available from the corresponding author upon reasonable request.

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