1: Spine. 2005 Nov 15;30(22):2516-22.Click here to read Links
Alendronate inhibits spine fusion in a rat model.

Hospital for Special Surgery, New York, New York 10021, USA. huangr@hss.edu

STUDY DESIGN: A posterolateral lumbar fusion model in rats.
OBJECTIVE: To study the effects of alendronate on posterolateral lumbar fusion in rats.

SUMMARY OF BACKGROUND DATA: To our knowledge, there are no studies that show a significant inhibition of manual palpation-assessed spine fusion by alendronate.

METHODS: A total of 75 Sprague-Dawley rats underwent intertransverse fusion with 7-tailbone autograft at L4-L5. Animals received saline (control), alendronate equivalent to human dose (dose1, 5 microg/kg/day), or 10 times the human dose (dose10, 50 microg/kg/day) via subcutaneous osmotic pumps starting the day of surgery. Eight weeks after surgery, animals were euthanized, and fusion was assessed by manual palpation. Radiographic area and optical density of fusion masses were calculated. Histomorphometry was used to assess the percentage area of fusion masses occupied by bone or marrow tissues. RESULTS: Manual palpation fusion rates were lower in alendronate groups (50% and 40%, respectively) than in the control group (95%, P = 0.002). Interobserver and intraobserver kappa values were high (0.97-1.00). There were dose-dependent and statistically significant (P < 0.001) increases in fusion mass area and optical density with increasing alendronate dose. Fusion masses in dose10 animals had significantly higher percent area of bone tissue (P = 0.01) and lower percent area of marrow elements (P < 0.001) when compared to control animals.

CONCLUSIONS: Alendronate inhibits spine fusion in rats. Fusion masses in alendronate-treated animals appeared radiographically larger and denser than those in control animals despite lower fusion rates. Quantitative histomorphometry confirmed that alendronate inhibited bone graft resorption and incorporation. We recommend that patients undergoing spine arthrodesis should not take alendronate until fusion is achieved.

PMID: 16284589 [PubMed - indexed for MEDLINE]
Spine. 2005 May 15;30(10):1116-21.Click here to read Links
The influence of alendronate treatment and bone graft volume on posterior lateral spine fusion in a porcine model.
* Orthopedic Department, Institute for Experimental Clinical Research, Aarhus, Denmark. xueqingyun@hotmail.com

STUDY DESIGN: An experimental animal study with randomized, paired control design was conducted using a porcine model.

OBJECTIVES: The aim of this study was to evaluate the influence of alendronate treatment and the significance of different amounts of bone graft on posterior lateral spine fusion.

SUMMARY OF BACKGROUND DATA: Treatment with bisphosphonates inhibits osteoclast-induced bone resorption and increases bone quality and density. It has been widely used clinically for treatment of osteoporosis. Bisphosphonates have been reported to elongate the callus remodeling process during fracture healing. Bisphosphonate treatment may modify bone graft healing and the remodeling process in spine fusion. The bone resorption phase exists during the healing process. Extensive bone graft resorption could reduce the basis for new bone formation, which could be an important factor for failure of spine fusion. Furthermore, different amounts of initially applied bone graft may influence spine fusion rate and bone graft incorporation process.

METHODS: Twenty-two pigs were included in the study. Eleven pigs in the treatment group received alendronate 10 mg/day p.o. for 3 months after surgery. The other 11 pigs received no bisphosphonate and served as control group. Posterior lateral fusion with the CD Horizon system was performed on the lumbar spine using different amounts of autograft (4 g on one side and 8 g on the other side) in all animals. The fusion was evaluated using radiograph, CT scan, and histomorphometry at 3 months after operation.

RESULTS: There was no statistical difference in either fusion rate or fusion mass volume between the two groups. The fusion rate based on radiograph was 75% on the 8-g autograft side and 45% on the 4-g side (P < 0.05). The mean volume of fusion mass was 2.36 cm3 on the 4-g side and 3.29 cm3 on the 8-g side (P < 0.01). No difference was found in either trabecular bone volume or fusion rate between treatment and control groups using histologic evaluation.The treatment group showed a higher fibrous tissue volume(P < 0.05), higher proportion of woven bone structure(P < 0.001), and lower bone marrow volume (P = 0.088) in the fusion mass. Different amounts of bone graft did not change the tissue composition of the fusion mass.

CONCLUSIONS: Alendronate treatment in this study decreased fusion mass remodeling without inhibiting fusion rate. Increased amounts of autologous bone graft could improve the fusion rate in this experimental spine fusion study.

PMID: 15897823 [PubMed - indexed for MEDLINE]

: Spine J. 2004 Jan-Feb;4(1):36-43. Links
The effect of alendronate sodium on spinal fusion: a rabbit model.

Department of Orthopaedic Surgery and Rehabilitation, Walter Reed Army Medical Center, Washington, DC 20307, USA. Ronald.Lehman@NA.AMEDD.ARMY.MIL

BACKGROUND CONTEXT: Bisphosphonates affect bone remodeling and increase bone mass through the inhibition of osteoclasts. Their effect on osteoblasts, and the balance between osteoblastic and osteoclastic activity on bone turnover and healing, is not completely understood. Specifically, the effect of bisphosphonates on spinal fusion has yet to be determined. With the increasing use of bisphosphonates in the elderly population, this effect needs to be delineated.

PURPOSE: To evaluate the effect of alendronate sodium after an intertransverse process spinal fusion in a rabbit model.

STUDY DESIGN/SETTING: Randomized double-blinded in vivo study of the effect of alendronate sodium in a spinal fusion model.

METHODS: Fifty New Zealand white rabbits underwent a posterolateral L5-L6 intertransverse process arthrodesis with autogenous iliac crest bone graft. The rabbits were then randomly divided into two groups. Group I received 3 cc of saline placebo per oral gavage, and Group II received 200 micrograms (approximately 0.05 mg/kg/day) of alendronate sodium dissolved in 3 cc of saline per day for 8 weeks. Upon completion, the rabbits were sacrificed and the lumbar spines harvested, radiographed and graded for motion across the fusion site with manual palpation. Two independent pathologists then prepared and sectioned each left and right fusion mass. Three random x10 fields were examined and graded for both the cephalad and caudad ends of each section (516 fields). Fusion quality was graded using an established histological scoring scale (score 0 to 7 based on fibrous and bone content of the fusion mass).

RESULTS: Two rabbits died on the day of operation, and 48 rabbits survived the operation. Five additional rabbits died within the first 2 postoperative weeks. Thus, 43 rabbits (21 in Group I, 22 in Group II) completed the 8-week course of treatment. Grading each side separately, 26 of 42 fusion masses (62%) in Group I and 24 of 44 fusion masses (55%) in Group II had radiographic evidence of fusion (p=.76). With gross palpation, 11 of 21 motion segments (52%) in Group I versus 13 of 22 motion segments (59%) in Group II were determined to have a solid fusion (p=.76). Histologically, Group I had a higher median score (6.0; range, 0 to 7 vs. 1.0; range, 0 to 7; p<.0001) and a higher fusion rate (76% vs. 45%; p=.004) than Group II.

CONCLUSIONS: Alendronate sodium appears to inhibit or delay bone fusion in a rabbit model. Presumably, this occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing. These findings suggest that a discontinuance of alendronate sodium postoperatively during the acute fusion period may be warranted.

PMID: 14749192 [PubMed - indexed for MEDLINE]