After menopause, depletion of estrogen increases bone turnover, and the rate of osteoclastic resorption exceeds the rate of osteoblastic formation, resulting in a loss of bone mass8)
. Based on this observation, patients with osteoporosis and osteopenia may not be good candidates for fusion surgery due to instrument or fusion failure following surgery for traumatic fracture and degenerative spinal disease. It is estimated that more than 200000 spine fusion procedures are performed each year in the United States3)
. Posterior lumbar arthrodesis is the most common procedure performed, and failure to achieve a solid bony union (nonunion) occurs in 10-40% of patients with a single-level fusion and more frequently when multiple levels are attempted11,12,27)
Various kinds of drugs used in the treatment of osteoporosis, such as bisphosphonates, parathyroid hormone, estrogen, selective estrogen receptor modulators, calcitonin, and vitamin D, are options for inducing osteoporotic fracture healing14,17,20,29,36,37)
. However, whether these drugs are effectively help the patients with osteoporosis or osteopenia is unclear. Lehman et al.28)
reported that alendronate sodium inhibited or delayed bone fusion after intertransverse process spinal fusion in a rabbit model. Presumably, this resulted from uncoupling of the balance between osteoclastic and osteoblastic activities inherent in bone healing. By contrast, Nagahama et al.31)
found that favorable mechanical circumstances provided by alendronate overcame its detrimental biological effects on the healing process after spinal fusion. Therefore, they recommended that osteoporosis patients undergoing spinal fusion take bisphosphonates throughout the postoperative period. In addition, at low intermittent pulsatile doses, parathyroid hormone administration increases bone formation in rats7,26,33)
. However, the clinical use of parathyroid hormone has several disadvantages, such as the need for daily subcutaneous injection in the abdomen or thigh, and the expense relative to other drugs4)
Calcium is one of the most important nutrients in the healing of bone fractures30)
. Some studies have reported on the structural changes induced by calcium treatment during fracture healing6,15,19,37)
. However, there is still lack of knowledge about the effects of calcium on spinal bone fusion with osteoporosis. Thus, we examined the effect of calcium supplementation on spinal bone fusion in the ovariectomized rat. In the present study, 3D-µCT images showed significant changes in the structural characteristics of the fusion mass in animals treated with calcium. Calcium-treated animals had significantly more abundant fusion volumes compared with the control animals. Calcium intake increases bone formation and decreases bone resorption activity at the graft site, which seems to have beneficial effects on graft bone healing, especially in bone remodeling after new bone formation30)
. In our study, the serum level of osteocalcin, an osteoblast marker, peaked 4 weeks after surgery in the OVX-Ca rats and was higher at 4 and 8 weeks after surgery in OVX-Ca group than in the control group () (p
<0.05). This finding suggests that calcium intake has positive effects on osteoblast activation after fusion surgery in the osteoporotic condition. The level of serum CTX, a bone resorption marker, increased in both groups, peaked 4 weeks after surgery, and then decreased from 4 to 8 weeks after surgery. Serum CTX level was lower in the OVX-Ca group than in the control group throughout the postoperative course () (p
<0.05). These findings propose that calcium agents shifted the bone formation/resorption balance in a positive direction during the bone graft fusion process.
These results are consistent with previous findings in experimental osteoporotic-fracture models6,15,21,25,37)
. Ahmad et al.37)
studied the effects of calcium supplementation on fracture healing of osteoporotic bone in ovariectomized rats. Calcium supplements appeared to improve fracture healing of osteoporotic bone. Half of the ovariectomized rats were given calcium supplements throughout the healing phases, and this may explain the similar radiological evidence of fracture healing in the supplemented and sham-operated rats.
In ovariectomized rats, compared to the Sham group (non-operated rats), serum ionized-calcium levels showed no significant differences in other experimental study16)
. Therefore, we did not compare the sham group with the calcium supplementated group. In this study, after fusion surgery, the serum calcium concentration was significantly higher in the OVX-Ca group than in the control group for postoperative period (p
Mechanical strength of the healed fractured bone is a reliable test of the bone's recovery to its normal strength2,13)
. In our study, we used the three-point bending test. The fused vertebrae in the OVX-Ca group could withstand a 50% higher maximal load compared with the control group () (p
<0.01). These results suggest that calcium intake can increase the mechanical strength by increasing the fusion mass volume. These positive effects on bone formation correspond to those of other studies showing that drugs used to treat osteoporosis augment spinal fusion mass volume in experimental models14,33,38)
. However, we did not perform pathological examination of the bone mass, and this finding does not necessarily indicate an improvement in the fusion mass quality. The fusion mass quality should be evaluated in future studies.
In the present study, we attempted to answer the key question about the relationship between calcium intake and spinal fusion in osteoporosis : Specifically, is the addition of dietary calcium sufficient to provide a clinical advantage for patients undergoing spinal fusion in osteoporosis? Our findings suggest that calcium supplementation improves mechanical strength and that this may overcome its complicated biological effect on the healing process in spinal fusion. We recommend that osteoporosis patients undergoing spinal fusion should receive an adequate intake of calcium throughout the perioperative period.
Finally, several questions remain to be answered in future research. 1) For how long should patients take calcium before and after spinal fusion surgery to improve the strength of vertebral bodies? 2) What is the optimal dose of calcium to increase the bone fusion mass? 3) Does the bridging bone formed during calcium treatment lead to superior bone quality? These questions will form the basis of our future studies.