OVCFs are common in patients with osteoporosis 13 and can be treated satisfactorily with minimally invasive surgery. 14 NVCFs are common and serious complications in patients with OVCFs that can lead to hospitalization. No studies have included BMD in prediction models, so we developed and validated a nomogram in the present study to predict the risk of re-fracture after PKP surgery.
Osteoporosis is a systemic bone disorder characterized by low bone mass and destruction of bone tissue microarchitecture, leading to increased bone fragility and susceptibility to fracture. 15 The World Health Organization uses BMD and the T-score to define osteoporosis. The T-score is a standard deviation representing the difference between the patient and the mean BMD of healthy young adults. A T-score < -2.5 is defined as osteoporosis, and a T-score between − 1 and − 2.5 is defined as osteopenia. The results of our multivariate analysis suggest that low BMD and age are independent risk factors for NVCF, and that BMD is negatively associated and age is positively associated with the development of NVCFs. In older women, increased bone remodeling in cancellous and cortical bone with negative remodeling balance leads to bone loss and destruction of bone microstructure. Cancellous bone exhibits trabecular thinning and trabecular loss, whereas cortical bone exhibits reduced cortical thickness and increased cortical porosity. In older men, osteoporosis is primarily associated with reduced bone formation and low bone turnover. 16 BMD decreases with age, 17 and low BMD is a factor in surgical vertebral re-fracture that cannot be neglected. 7 An analysis of bone tissue and serum bone turnover markers in 206 patients by Qi et al. 18 showed that patients with low BMD had more necrotic bone tissue and lower bone turnover markers after fracture, indicating that patients with low BMD have poorer bone healing capacity. In addition, patients with osteoporosis have sparse trabeculae, significantly reduced vertebral body strength and compression resistance, and more severe vertebral body collapse under the same external force, making NVCFs more likely.
As shown in Table 2, lack of anti-osteoporosis treatment is a major risk factor for development of NVCFs after PKP. Anti-osteoporosis treatment reduces the progression of osteoporosis and prevents the development of NVCFs. 19 In the training cohort, 98 control patients were given anti-osteoporosis treatment (51%), compared to seven NVCF patients (22%). Bisphosphonate and denosumab are first-line agents in the treatment of osteoporosis. 20 Bisphosphonate causes a progressive increase in BMD that plateaus after 3–4 years of treatment, while denosumab increases BMD more dramatically and persists for 10 years. 20 In a 3-year phase III clinical trial, denosumab reduced vertebral fractures by 68%. 21 Routine anti-osteoporosis treatment is recommended for post-PKP patients without contraindications.
Our study suggests that low BMI is a risk factor for NVCF. The effect of high BMI on vertebral fractures is controversial. In a study of osteoporotic fractures, high BMI was a protective factor for vertebral fracture due to the protective effect of higher adiposity. 22 Obese menopausal women tend to have higher estrogen levels, resulting in high BMD and low bone turnover and contributing to a lower risk of fracture. 23 However, it is hypothesized that obesity produces a pro-inflammatory/pro-oxidative state in bone, inhibiting bone formation and inducing bone resorption. 24 In addition, low BMI leads to NVCFs associated with low BMD. 25 Recent studies have suggested classifying Chinese adults with a BMI < 20 kg/m2 as malnourished. 26 Calcium and vitamin D are important nutritional factors in the management of osteoporosis. Calcium is an essential substance for bone mineralization and provides hardness and strength to bone. 27 Vitamin D regulates calcium homeostasis, and vitamin D deficiency also leads to osteomalacia. Studies have shown that malnutrition can promote the progression of osteoporosis. 28
In the present study, high AVHRR was considered an independent risk factor, consistent with previous findings. 29–31 In addition, we report for the first time that low AVH is also a risk factor. Patients with low preoperative vertebral body height tend to have higher vertebral body recovery rates. The relationship between high AVHRR and vertebral fracture has not been clearly explained. One hypothesis is that excessive vertebral body height recovery leads to increased tension of paravertebral soft tissues, which increases the mechanical load on the augmented vertebral body or the instability of the fractured segment. 30 Heo et al. 32 suggested that excessive vertebral body recovery may also increase the progression of osteonecrosis. PKP is not a procedure for correcting a deformity, but rather a minimally invasive procedure used to reduce the pain experienced by patients with NVCFs. Therefore, moderate but not excessive expansion of the fractured vertebral body is recommended.
Lack of simultaneous contact of bone cement with the upper and lower plates is an independent risk factor for vertebral body re-collapse. A retrospective study 33 found that NVCFs occurred 4.6 times more frequently in patients with bone cement leakage than in those without leakage. Other studies 34,35 have confirmed that bone cement leaks through the ruptured endplates into the intervertebral disc, which results in altered peri-vertebral stresses and reduced disc cushioning. In addition, the distribution of bone cement in the treated vertebral body is considered a risk factor for vertebral re-fracture. 36 The results of a cohort study showed that adequate contact of bone cement with the upper and lower plates significantly reduced the risk of vertebral re-compression. 37 When bone cement contacted only the upper or the lower plate, the strength of the vertebral body was increased by only a factor of 2, but when the cement contacted both the upper and lower plates, the strength was increased by a factor of 8–12, significantly improving stress transfer. 38
Lasso regression has the advantages of univariate analysis, as it can solve the problem of multicollinearity among variables. However, our study still included some limitations. First, the study was retrospective in nature and the effects of missing data and case selection bias were inevitable. Second, although the nomogram was validated in a validation cohort, the data were derived from the same hospital and were not validated through multiple centers in other regions and countries, which may limit the use of the model in some hospitals. Therefore, further validation in large-sample multi-center studies is needed in the future.