This retrospective clinical data analysis collected 60 patients with OVCF hospitalized in the orthopedics department in the First Affiliated Hospital of Hebei North University in China from September 2018 to September 2019. The study was approved by the medical ethics committee of the First Affiliated Hospital of Hebei North University.

Inclusion criteria: 1) Age ≥ 65; 2) Preoperative BMD T value ≤ −2.5SD; 3) Diagnosis of osteoporotic single vertebral (T₅-L₅) compressive fractures, fracture stability without spinal cord and redundant nerve damage, and the patient’s medical history ≤ 2 weeks; 4) Patients who had not used relevant medicine such as zoledronic acid or teriparatide continuously for more than 3 months (short-term users, who could be enrolled after a 1-year washout period); 5) All had received surgical treatment for PKP; 6) They were followed for at least 1 year.

Exclusion criteria: 1) Patients with non-primary OVCF; 2) Patients with other pathological compression fractures of the thoracolumbar spine due to bone metastasis of malignancy; 3) Patients with long-term systemic use of glucocorticoids in the previous 1 year and prior treatment with oestrogen, raloxifene or calcitonin within 3 months.

SPSS20.0 statistical software was used to analyze the sample size required in the study. The presupposed medium effect size was f = 0.25 (Cohen, 1988), the statistical power was 1 − β = 0.8, and the significance level was α = 0.05. The results showed that at least 53 patients were needed in each group. Because it was a single centre study and time constraints, a total of 60 patients were taken conveniently for this study. They were divided into zoledronic acid (group A, n = 20), Teriparatide (group B, n = 20) and zoledronic acid + Teriparatide (Group C, n = 20).

SPSS 20.0 statistical software was used to analyze the data of the 3 groups. The data of the 3 groups were consistent with the normal distribution and the homogeneity of variance. The comparison between the groups was performed by analysis of variance (ANOVA). If there were differences between the groups, the LSD-t test was used. The comparison between the groups was performed by paired t-test. P < 0.05 was regarded as the difference with statistical significance.

60 cases were enrolled in the experiment, 20 cases in group A, 20 cases group B and 20 cases in group C. There were no significant differences in age, gender and distribution of diseased vertebrae among the three groups (P > 0.05) (Table 1). There were no significant differences in BMD, PINP and β-CTX before treatment (P > 0.05) (Table 2). There were no lost cases, missed follow-up cases and death cases during the follow-up period.

BMD in the 3 groups increased at 6 months after treatment, but the differences were not statistically significant (P > 0.05) (Table 3). And there was no significant difference between the 3 groups (F = 3.93, P = 0.26). Compared to pre-treatment, BMD in the 3 groups increased significantly at 1 year after treatment (P < 0.05) (Table 3). And there was significant difference between the 3 groups (F = 6.79, P < 0.05). In terms of improving BMD, group C was better than group B, and group B was better than group A (Table 4).

Note: a: comparison between 6 months pro-treatment and per-treatment; b comparison between 1 year pro-treatment and per-treatment.

The PINP of group A at 6 months and 1 year after treatment was lower than that before treatment, and the difference was statistically significant (P < 0.05). The PINP of group B and group C at 6 months and 1 year after treatment was higher than that before treatment, and the difference was statistically significant (P < 0.05) (Table 3). There was significant difference among the 3 groups at 6 months after treatment (F = 9.26, P < 0.05). In terms of improving PINP, the PINP of group B was better than that of group C and the PINP of group C was better than that of group A at 6 months after treatment. There was significant difference among the 3 groups at 1 year after treatment (F = 8.48, P < 0.05). In terms of improving PINP, the PINP of group B was better than that of group C and the PINP of group C was better than that of group A at 1 year after treatment (Table 4).

Compared to pre-treatment, β-CTX in the 3 groups increased at 6 months and 1 year after treatment (P < 0.05) (Table 3). There was significant difference among the 3 groups at 6 months after treatment (F = 6.38, P < 0.05). In terms of improving β-CTX, the β-CTX of group A was better than that of group C and the β-CTX of group C was better than that of group B at 6 months after treatment. There was significant difference among the 3 groups at 1year after treatment (F = 7.26, P < 0.05). In terms of improving β-CTX, the β-CTX of group A was better than that of group C and the β-CTX of group C was better than that of group B at 1 year after treatment (Table 4).

There were no significant differences in the incidence of fever, gastrointestinal reactions and myalgia among the 3 groups (P > 0.05). And the incidence of recurrent fracture was significantly different (P < 0.05). It was higher in group A than in group B and group C (t = 4.33, P = 0.04; t = 7.06, P = 0.01), and there was no significant different between group B and group C (t = 1.03, P = 0.50) (Table 5).

About 50% of OP fractures occurs in the spine, and the thoracolumbar spine is the most common [2] [13]. From the perspective of mechanics and biology, experts, like Ren, think that the probability of thoracolumbar vertebral compression fracture is higher, and patients with thoracolumbar vertebral fracture have higher risk than other vertebral fractures under the same clinical intervention after operation [7]. It is consistent with the data of this study (37/60, 61.67%). Research data showed that the vast majority of OVCF patients (44/60, 73.33%) were not definitely diagnosed as OP before admission. The discovery of OP mostly originated from the first fracture caused by OP [3] [6]. Microscopically, OP refers to the decrease of normal mineralized bone mass per unit volume, and the parallelism decrease of bone matrix and mineral salts [2] [5] [13]. In 2001, the National Institutes of Health (NIH) proposed a macro definition of OP, which emphasizes the decrease of bone strength and the increase of fracture risk, that is, OP not only reduces the amount of phalangeal bone, but also decreases the mechanical properties [1] [13]. Regular monitoring of BMD, assessment of fracture risk and active intervention in the process of OP can effectively reduce

the prevalence of OVCF [13]. The data of this study showed that there were 35 female patients (35/60, 58.33%) in OVCF patients, which was lower than that of large sample data [3] [4]. It was related to the selection of patients over 65. With the growth of age, postmenopausal women with primary osteoporosis enter the elderly primary osteoporosis after about 5 - 10 years, that is, the majority of OVCF patients over 65 belong to the elderly OVCF [13]. Therefore, the gender difference is not obvious. At the same time, OP patients over 65 belong to low transformation type, which can eliminate the bias of different bone metabolism types in clinical data observation.

At present, the diagnosis of OP mostly depends on the clinical symptoms and BMD examination [13] [14] [15]. BMD can reflect 70% of the bone mass, which is the gold standard for the diagnosis of OP [4]. However, the value change of BMD has a lag period of 6 - 12 months, and the sensitivity is low, which cannot provide effective help for the early diagnosis of OP [16] [17]. At the same time, BDM cannot reflect the process of bone turnover and bone metabolism, and it cannot provide evaluation for the short-term efficacy of clinical medication [17] [18]. Therefore, it cannot provide timely help for the selection of clinical medication. In this study, there was no significant difference in BMD at 6 months after treatment, but significant differences in PINP and β-CTX can be seen. PINP and β-CTX are the latest clinical indicators of bone metabolism [19]. Compared with BMD, PINP and β-CTX have better specificity and is the markers of bone formation and bone resorption [20] [21]. They are of great significance in evaluating OP, preventing and treating OVCF. PINP is expressed and released by activated osteoblasts, which is a sensitive indicator of bone formation [22]. The International Symposium on osteoporosis suggested that PINP should be used as a specific and sensitive indicator of bone formation [23]. β-CTX is a sensitive indicator of bone resorption. Relevant clinical studies have shown that β-CTX can be used to monitor the timeliness and efficacy of treatment in patients with osteoporosis [24]. This study shows that although zoledronic acid combined with teriparatide in the prevention of recurrent fractures has no significant difference with teriparatide monotherapy group, its improvement in BMD, β-CTX is still better than teriparatide monotherapy group. The follow-up time can further extend to observe and count the rate of recurrent fractures, which aims to draw the final conclusion.

Clinical data shows that the rate of recurrent fracture after PKP is as high as 25%. If the patients do not receive standardized anti-OP treatment within 3 years, the rate of recurrent fracture will reach 50% [25] [26]. At the same time, the recurrent fracture can further aggravate the damage of centrum and affect the prognosis of OVCF, which is a problem that OVCF patients must face [27]. At present, it is believed that it is closely related to stress increases of adjacent vertebrae which cause by bone cement strengthening the hardness of diseased vertebrae, and it is also related to ineffective treatment [5] [27]. The latest view is that recurrent fracture after OVCF is one of the manifestations of OP’s natural progress [28]. Therefore, ineffective treatment for OP is an important risk factor for fracture recurrence after PKP in OVCF patients. In this clinical study, there was no statistically significant difference in the distribution of diseased vertebrae in each group. PKP surgery can restore the height of diseased vertebrae as much as possible. Meanwhile, single diseased vertebrae and bilateral approaches are selected to make the distribution of bone cement in centrum satisfactory and as similar as possible. And the bias caused by poor recovery of vertebral height and different degree of bone cement enhancement is excluded. The data showed that the recurrent fracture rate (7/60, 11.67%) was lower than the literature data, which may be related to the standardized anti-OP treatment in this study [5] [13]. And it indirectly proved that the natural process of OP is an important reason of recurrent fracture.

Zoledronic acid can inhibit the activity of osteoclasts through antagonistic effect to inhibit bone absorption and reduce the incidence of fracture. It has strong adsorption, and low medicine loss rate [29] [30]. The medicine can be absorbed by bone tissue again. The medicine efficacy cycle is long, so it only needs to be injected once a year. The patient’s compliance is high [10] [31]. Teriparatide is an active fragment of parathyroid hormone, and it is an inhibitor of bone resorption [32] [33]. It can promote bone formation, improve BDM and reduce the risk of fracture [34]. At the same time, it has been clinically proved that it can be used not only for the treatment of osteoporosis, but also for promoting fracture healing [35]. Clinical data shows that Teriparatide is superior to zoledronic acid in improving BMD in OP patients. The sequential therapy based on the bone remodeling of physiological cycle has not achieved good clinical efficacy, even it is not better than the single use of anti-resorption medicine [36] [37]. Clinical data shows that there is no significant difference in adverse reactions between multiple anti-OP medicine combined with sequential therapy, which can produce greater superposition and synergistic effect, but the best combined sequential therapy has not been determined yet [37] [38]. Zoledronic acid combined with teriparatide may weaken the anabolism of teriparatide. Relevant clinical studies have shown that zoledronic acid combined with teriparatide has no obvious advantage over teriparatide in increasing BMD [39]. However, in an experiment of zoledronic acid combined with teriparatide after lumbar spinal fusion in ovariectomized rats, it can significantly improve the quality of bone fusion, and it is clinically proved to be effective [9]. At the same time, studies have shown that zoledronic acid combined with teriparatide can significantly reduce the rate of recurrent fractures compared with zoledronic acid [8]. Although the combined use in this clinical study has excellent performance in improving BMD, it cannot effectively reduce the incidence of recurrent fractures. It may be related to the smaller data sample and shorter follow-up time. Meanwhile, the research shows that the choice of OP treatment medicine should be based on bone metabolic markers [24] [40]. Low conversion medicine are mainly promoting bone metabolism, while high conversion medicine are mainly inhibiting bone resorption [40]. The results show that zoledronic acid combined with teriparatide is better than the single medicine group in improving bone metabolism markers PINP and β-CTX. However, the follow-up time is only one year, which may cover up some data.