Objective: To explore the clinical efficacy of Zoledronic Acid Injection in the treatment of postmenopausal osteoporosis with different bone turnover rates. Methods: A total of 63 patients diagnosed with postmenopausal osteoporosis were included in this study. Each patient was administrated 5 mg/100mL Zoledronic Acid (Aclasta) intravenously once and then given a one-year prescription of 600 mg/d oral Caltrate. The bone turnover parameters (PINP, β-cross, N-MID) were measured prior to the injection of Zoledronic Acid while the bone mineral density (BMD) and the pain scores of each patient were tested before treatment and after the one-year medication. On this basis, the patients were divided into several groups according to their bone turnover rates for intergroup comparison of treatment outcomes. Results: BMD results and pain scores of all participants were significantly improved at different levels after treatment. However, these improvements had no significant differences between the patients with high and low bone turnover rates. Conclusion: Zoledronic Acid Injection can relieve bone pain, enhance the quality of life and increase the BMD in patients with postmenopausal osteoporosis, regardless of the bone turnover status.
Osteoporosis (OP) is commonly seen in the middle-aged and elderly population in China. It is caused by a variety of factors featuring a decrease in bone mass and a deterioration in bone microarchitecture, which elevates the risk of fracture and fracture-prone metabolic bone diseases (MBDs). The clinical manifestations of OP mainly include pain, fracture, humpback and height loss. Considering the high mortality and disability rates, OP treatment and management has become a major issue in the public health sector [
The clinical data of 63 postmenopausal patients with osteoporosis who presented at our osteoporosis outpatient clinic from January 2016 to December 2017 were collected and analyzed in this study. All participants were postmenopausal women aged between 50 and 80 (mean age = 66.0 ± 8.0). Prior to the initial diagnosis, dual-energy X-ray absorptiometry (DXA) was used to test the bone mineral density of lumbar spine and femur, with the measured values being adopted as diagnosis and inclusion criteria. Patients were eligible for inclusion if the total lumbar spine (L1 - L4) bone mineral density value was no greater than −2.5, or T-score was below −1.0 with preexisting fragility fractures, definite systemic symptoms such as back pain or height loss, and normal 25(OH)D. Exclusion criteria: 1) Previous use (within six months before treatment) of estrogen, glucocorticoid (GC), calcitonin and other bisphosphonates (BPs) that might influence bone metabolism; 2) diabetes and endocrine disorders of thyroid, parathyroid, adrenal gland or gonad; 3) secondary osteoporosis; 4) an allergy to Zoledronic Acid.
Zoledronic Acid (5 mg in 100 mL ready-to-infuse solution) is administrated intravenously, followed by the oral medication of 600 mg/d calcium carbonate D3 (Caltrate) for one year. The patients were required to get regular sun exposure, namely basking in the sun for half an hour between 11:00 and 15:00, twice a week. The Zoledronic Acid (Aclasta) prescribed for the patients is produced by Novartis. It is a once-yearly injection that provides fracture protection in postmenopausal osteoporosis.
The following parameters were documented: pre-treatment bone turnover parameters (PINP, β-cross, N-MID), bone mineral density of lumbar spine and femur and bone pains before and after treatment. All bone turnover parameters were tested after an overnight fast by the clinical laboratory of our hospital; BMD was measured by dual-photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DXA); during treatment, the patients were recommended to pay follow-up visits to the hospital to diagnose whether they had fresh fragility fractures.
In terms of bone pains, the Visual Analogue Scale (VAS) was used for pain assessment. VAS (4-point scale): 1) No pain; 2) Mild pain (without affecting sleep); 3) Moderate pain (affecting sleep at a tolerable degree); 4) Severe pain (intolerable, unable to fall asleep).
1) Bone pains and fresh fractures were tested after the one-year treatment.
2) The BMD (g/cm2) and VAS scores before and after treatment were documented and analyzed.
3) The patients were divided into different groups by each bone turnover parameter according to the corresponding normal range specified by our hospital (PINP: 0.00 - 36.4 ng/ml; β-cross: 0.30 - 2.00 ng/ml; N-MID: 14.00 - 46.00 ng/ml). Specifically, the patients were respectively divided into a normal PINP group and an abnormal group with higher PINP levels, a normal β-cross group and an abnormal one with lower β-cross levels, and a normal N-MID group and an abnormal one with lower N-MID levels to analyze the improvement in BMD and VAS score.
The statistical analysis software SPSS22.0 was used for data analysis. Measurement data were expressed in the form of “mean ± standard deviation (x ± s)” and the t-test was applied to the intragroup comparison. Besides, the chi-squared test was designed for the comparison of enumeration data. P < 0.05 indicated a difference of statistical significance.
After being treated for one year, no fresh fractures were detected in the 63 patients during follow-up visits. As shown in
As shown in
Neither fresh fragility fractures nor obvious adverse reactions were detected in the participants throughout the course of treatment.
Metabolic activity brings about dynamic changes and constant remodeling of bone tissue while OP is caused by an increase in osteoclasts and loss of BMD,
Number of Cases | Age | Pre-Treatment L2-4BMD | Pre-Treatment VAS | P1 | P2 | P3 | |
---|---|---|---|---|---|---|---|
PINP→ | 37 | 66.7 ± 8.3 | 0.827 ± 0.153 | 2.18 ± 0.896 | |||
PINP↑ | 26 | 65.0 ± 7.6 | 0.858 ± 0.110 | 1.88 ± 0.833 | 0.401 | 0.376 | 0.18 |
β-CROSS↓ | 36 | 67.0 ± 8.6 | 0.842 ± 0.150 | 2.19 ± 0.92 | |||
β-CROSS→ | 27 | 64.6 ± 7.0 | 0.836 ± 0.119 | 1.89 ± 0.801 | 0.248 | 0.868 | 0.173 |
N-MID→ | 32 | 67.5 ± 8.5 | 0844 ± 0.142 | 2.19 ± 0.931 | |||
N-MID↑ | 31 | 64.4 ± 7.3 | 0.836 ± 0.134 | 1.94 ± 0.814 | 0.135 | 0.792 | 0.258 |
Note: ↓, →, and ↑ respectively denote subnormal, normal and above-normal levels of bone turnover parameters. P1, P2 and P3 respectively express the P-values based on the comparison of the age, pre-treatment L2-4BMD, pre-treatment VAS between groups which divided by different levels of bone turnover parameters.
Number of Cases | Before Treatment | After One-Year Treatment | P-Value | |
---|---|---|---|---|
BMD (g/cm2) | 63 | 0.840 ± 0.137 | 0.883 ± 0.151 | 0.001 |
VAS score | 63 | 2.06 ± 0.878 | 1.7 ± 0.647 | 0.026 |
Number of Cases | BMD Increase (g/cm2) | VAS (Post-Pre) | P1-Value | P2-Value | |
---|---|---|---|---|---|
PINP→ | 37 | 0.047 ± 0.080 | −0.243 ± 0.76 | ||
PINP↑ | 26 | 0.045 ± 0.058 | −0.192 ± 0.800 | 0.096 | 0.799 |
β-CROSS↓ | 36 | 0.044 ± 0.084 | −0.222 ± 0.800 | ||
β-CROSS→ | 27 | 0.050 ± 0.052 | −0.222 ± 0.751 | 0.744 | 0.999 |
N-MID→ | 32 | 0.051 ± 0.087 | −0.219 ± 0.792 | ||
N-MID↑ | 31 | 0.036 ± 0.050 | −0.226 ± 0.762 | 0.419 | 0.971 |
Note: P1-value, P2-value respectively express the P-values based on the comparison of the BMD increase, VAS (post-pre) between groups which were divided by different levels of bone turnover parameters.
which impedes bone matrix formation and calcium salts deposition and ultimately leads to increased bone resorption and imbalanced bone turnover―that is, bone resorption exceeds formation. In terms of the underlying pathogenesis, OP can be classified as primary and secondary. For the patients aged 60 and above, 56% have osteoporosis. Particularly, hip fractures contribute the greatest to morbidity and mortality among all osteoporotic fractures, with 20% of the patients died within a year after the hip fracture. With the population aging, osteoporosis becomes increasingly prevalent and imposes a national threat to public health. As such, anti-osteoporosis drugs are gaining wider clinical application. In addition, a great variety of anti-osteoporosis drugs targeting at different symptoms have been developed. For instance, Teriparatide works by stimulating new bone formation; BPs have an effect of inhibiting bone reabsorption [
It is well established clinically that BPs can prevent and treat OP by inhibiting osteoclast formation and bone reabsorption. The BP therapy is most often used to treat metabolic bone diseases (MBDs) featuring a significant increase in bone reabsorption, especially those with a high turnover rate [
Metabolic products, namely bone metabolic markers, are released during bone remodeling. Bone metabolic markers are clinical indicators of bone turnover status. In clinical practices, these bone metabolic markers indicate the bone formation rate greater than the bone reabsorption rate, or vice versa. Type I procollagen-N-propeptide (PINP) is a bone formation marker reflecting the changes of newly synthesized type I collagen, namely an indicator of bone formation. The bone turnover marker N-terminal midfragment osteocalcin (N-MID OC) is a bone-specific, calcium binding protein released by bone formation and resorption. β-Cross, as a bone resorption marker, is the degradation product of type I collagen C-telopeptides. β-Cross, PINP and N-MID are three bone markers recommended by the International Osteoporosis Foundation (IOF). Zoledronic Acid is a representative bone resorption inhibitor. In a study investigating the effect of Zoledronic Acid Injection on osteoporosis, it was found that Zoledronic Acid Injection, combined with regular calcium and Vitamin D supplements, could effectively reduce the N-MID, b-CTX and PINP levels and improve the bone turnover rate; apart from this, the bone reabsorption parameter N-CTX decreased more drastically than the bone formation parameter PINP, indicating a significant improvement in quality of life [
As an increasing number of bone turnover parameters extend their clinical application, it becomes a cause for concern whether the clinical efficacy of Zoledronic Acid varies in the treatment of osteoporosis with different bone turnover rates. In this study, the patients were divided into several groups by different bone turnover parameters for intergroup comparison and the differences showed no statistical significance. The study results suggested no statistically significant differences in the curative effect of Zoledronic Acid on osteoporosis with different bone turnover rates. This indicates that bone turnover parameters are neither appropriate criteria for the clinical application of Zoledronic Acid, nor reliable indicators in the assessment of its curative effect. In terms of osteoporosis, an increase in the bone turnover rate means a high bone turnover and rapid bone loss, regardless of the relationship between bone formation and bone reabsorption. This, combined with the BMD test, serves as the basis for an initial or follow-up anti-osteoporosis therapy. If relevant bone turnover parameters rise abnormally, the patient probably has secondary osteoporosis.
There were only 63 patients included in this study, and all patients were under observation for one year only. The results of the VAS are inevitably affected by the inherently subjective patients. Besides, the statistical analysis might be underrepresented because a relatively small number of patients were included in each group.
Neither severe side effects nor fresh fractures occurred during the course of treatment. It was demonstrated that Zoledronic Acid is efficacious in the treatment of postmenopausal osteoporosis with different bone turnover rates by reducing the loss of BMD and bone pains in the patients without triggering serious side effects.
The authors declare no conflicts of interest regarding the publication of this paper.
Jie, S.M., Deng, J.M., Lin, C.X., Cai, X.Z. and Cai, D.M. (2018) Curative Effect Analysis of Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis with Different Bone Turnover Rates. International Journal of Clinical Medicine, 9, 621-628. https://doi.org/10.4236/ijcm.2018.98052