Corinna C. Zygourakis, Darryl Lau, and Christopher P. Ames
The prevalence of osteoporosis is increasing as our population ages and lifespan increases. A recent study estimated that 53.6 million older U.S. adults had osteoporosis or low bone mass in 2010.1 In conjunction with this increase is a rise in spinal fractures and spinal deformity associated with osteoporosis. One group found that over half of women and nearly 15% of men over the age of 50 undergoing spine surgery had osteoporosis.2 Another retrospective review revealed that 10% of women undergoing scoliosis surgery had osteoporosis.3
Osteoporosis is associated with higher rates of complications, particularly in spinal surgery involving hardware.4,5 This is because many spinal fixation techniques rely on bone quality and adequate bone healing, which are impaired in osteoporosis. In an analysis of over one million patients undergoing cervical spine surgery in the National (Nationwide) Inpatient Sample (NIS), patients with osteoporosis stayed in the hospital for one day longer on average, had 30% costlier hospitalizations, and had a 1.5-times greater chance of requiring revision surgeries, as compared to patients without osteoporosis.6 It is therefore important for us to proactively identify, diagnose, and treat patients with osteoporosis before performing spine surgery.
Osteoporosis is defined as “a skeletal disorder characterized by compromised bone strength leading to an increased risk of fracture.”7 Clinically, it is diagnosed by the non-invasive assessment of bone mineral density (BMD) using the dual-energy X-ray absorptiometry, i.e., DEXA scan. More specifically, the DEXA scan uses X-rays to measure bone density at specific locations in the body, such as the lumbar spine, hip, and distal forearm.
World Health Organization (WHO) criteria defines BMD relative to the value for a normal healthy young adult: this is called the T-score. A T-score at the hip of -1 standard deviations (SD) or higher is normal; -1 to -2.5 SD characterizes osteopenia or low bone mass; a score of less than -2.5 SD defines osteoporosis.8 BMD can also be expressed relative to an age-matched healthy control (the Z-score), although the T-score is preferred for diagnostic use.8
Primary care guidelines recommend DEXA scans for all women at age 65 and men at age 70 in the absence of other risk factors.9 Screenings should be performed earlier in patients with risk factors that include low body weight, early menopause (before age 45), family history of osteoporosis, personal history of rheumatoid arthritis, inflammatory bowel disease or chronic obstructive pulmonary disease, and patients who take drugs such as glucocorticoids, proton pump inhibitors, or selective serotonin reuptake inhibitors.9
Despite these recommendations, many patients come to their spine surgeons without appropriate osteoporosis screening, and many spine surgeons do not routinely request DEXA scans. A recent survey revealed that only 60% of spine surgeons obtained DEXA scans before surgery for spinal fractures; 44% of surgeons checked DEXAs before instrumented fusion; and only 19% performed DEXA scans before non-instrumented fusions.10
Adequate calcium, vitamin D, and weight-bearing exercise are important for bone health in all patients.9 For those with osteoporosis, several medications are currently approved by the US Food and Drug Administration to increase bone strength by reducing bone resorption. These include two oral bisphosphonates, alendronate and risedronate, that specifically inhibit osteoclasts and thereby prevent bone breakdown. Non-oral options are denosumab (a RANKL inhibitor that prevents the development of osteoclasts), zoledronic acid (another bisphosphonate), and teriparatide (also known as Forteo®, a recombinant form of PTH that stimulates osteoblasts to build bone mass).9
Animal studies show that bisphosphonates induce the formation of large fracture calluses containing less mature bone.11-13 However, their overall effect on the mechanical strength of healed bone is unclear, as there is conflicting evidence from animal work.14-17 A meta-analysis of the eight randomized controlled trials looking at the effect of bisphosphonates on fracture healing for a variety of orthopedic procedures in humans found that bisphosphonate infusion after lumbar fusion may promote bone healing and shorten post-op fusion time.18 (See Table 5-1.)
|Lenehan et al., 198513||Dog||Low doses of ethane-1-hydroxy-1,1 disphophonate improve ultimate load at failure and flexural rigidity of fractured limbs|
|Nyman et al., 199312||Rat||Clodronate increases the calcium content of fracture calluses|
|Tarvainen et al., 199416||Rat||Clodronate delays fracture remodeling and does not improve bone strength|
|Nyman et al., 199611||Rat||Clodronate increases formation of new bone matrix, but it is not well organized compared to controls|
|Peter et al., 199615||Dog||Alendronate has no effect on union, strength, or mineralization of bone|
|Li et al., 200117||Rat||Long-term incadronate treatment delays fracture healing|
|Amanat et al., 200514||Rat||Single dose of pamidronate increases bone mineral content, volume, and strength of healing fractures|
|Xue et al., 201418||Meta-analysis of 8 clinical trials: 2,509 patients total||Bisphosphonates do not have a statistically significant effect on indirect bone healing; however, in spinal fusion surgery, bisphosphonates can promote bone healing and shorten time to fusion|
In addition to several animal studies showing that teriparatide accelerates and enhances spinal fusion in rats and rabbits,19-25 multiple clinical trials suggest that teriparatide is effective at promoting spinal fusion in humans and is superior to bisphosphonates.26 (See Table 5-2.) In one study of 57 postmenopausal women who underwent instrumented posterolateral lumbar fusion with local autograft, the rate of bone fusion was 82% in the group that received teriparatide versus 68% in the bisphosphonate group. Patients received both medications for 2 months before and 8 months after surgery. The average time to fusion was 8 months for the patients receiving teriparatide, compared to 10 months for those getting bisphosphonates.27 The same researchers also reported lower rates of pedicle screw loosening in 62 women with osteoporosis who underwent instrumented posterolateral lumbar fusion: 7-13% in the teriparatide group, versus 13-26% in the bisphosphonate group and 15-25% in the control not receiving either medication.28 They found higher rates of fusion and shorter time to bony fusion in patients getting teriparatide for longer periods of time: 92% fusion rate in patients receiving teriparatide for an average of 13 months versus 80% fusion in those getting teriparatide for an average of 5.5 months.29
Another group confirmed higher insertional torque on pedicle screws placed in patients receiving teriparatide for a minimum of one month before spinal fusion surgery.30 A study of 58 osteoporotic Japanese females undergoing adult spinal deformity surgery found lower rates of adjacent vertebral disease and implant or fusion failure, as well as better pain and ODI scores, in patients getting teriparatide versus bisphosphonates.31 Yet another group showed earlier fusion in patients on teriparatide as compared to bisphosphonates, although fusion rates were similar.32 (See Table 6-2.)
|Lawrence at al., 200625||Rat||There is a trend towards greater fusion rate with daily injections of parathyroid hormone|
|Abe et al., 200724||Rat||Intermittent parathyroid hormone enhances bone turnover|
|O’Loughlin et al., 200923||Rabbit||Intermittent parathyroid hormone increases posterolateral fusion success|
|Lehman et al., 201022||Rabbit||Teriparatide is associated with higher histologic fusion rates and less motion in flexion/extension, lateral bending and axial rotation|
|Ming et al., 201221||Rat||High-dose teriparatide has anabolic skeletal effects and significantly enhances spinal fusion rate|
|Qiu et al., 201320||Rat||High-dose parathyroid hormone enhances quantity of fusion callus, reduces healing time of posterolateral spinal fusion|
|Suguira et al., 201519||Rat||Intermittent teriparatide stimulates bone formation at the fusion mass and increases the fusion rate|
|Ohtori et al., 201227||57 women with osteoporosis who underwent 1-2 level spinal fusion||82% rate of bone union in teriparatide group vs. 68% in bisphosphonate group; average duration of bone union is 8 months in teriparatide versus 10 in bisphosphonate group|
|Ohtori et al., 201328||62 women with osteoporosis who underwent 1-2 level spinal fusion||7-13% incidence of pedicle screw loosening at 1 year in teriparatide group vs. 13-26% in risedronate group vs. 15-25% in control|
|Inoue et al., 201430||29 women with osteoporosis undergoing thoracolumbar fusions||Teriparatide injections beginning at least 1 month prior to surgery significantly increase the insertional torque of pedicle screws|
|Ohtori et al., 201529||45 women with osteoporosis who underwent posterolateral fusion||Longer duration of teriparatide treatment (>6 months) has higher bone union rate (92%) and shorter duration for bone union (7.5 months) compared to short-duration teriparatide treatment (fusion rate=80%, 8.5 months to union)|
|Cho et al., 201532||47 osteoporotic patients who underwent posterolateral interbody fusion||Teriparatide group has faster union (6.0 vs. 10.4 months) and higher bone mineral density scores than those getting bisphosphonates; no significant difference in overall fusion rate or clinical outcome|
|Seki et al., 201731||58 women with osteoporosis who underwent fusion for adult spinal deformity||Patients receiving teriparatide have lower rates of adjacent vertebral fractures and implant or fusion failure, and lower pain sores than those getting bisphosphonates|
PREOPERATIVE BONE OPTIMIZATION
Our preoperative bone optimization protocol incorporates the elements of the American Orthopedic Association’s “Own the Bone” program. These include (1) nutritional counseling: improving calcium and vitamin D intake, (2) physical activity counseling: promoting weight-bearing and muscle-strengthening exercises and fall prevention education, (3) lifestyle counseling: promoting smoking cessation and limiting excessive alcohol intake, (4) pharmacotherapy, (5) DEXA testing, and (6) communication with the referral physician and the patient to discuss their risk factors and recommendations for bone health treatment.33
In our adult spinal deformity practice, we routinely obtain DEXA scans on all patients undergoing fusion surgery. Any patients with hip and distal radius T-scores less than -2.5 are started on teriparatide 20 micrograms daily via subcutaneous injection. We delay elective surgery in order to provide patients with at least 2-3 months of teriparatide before surgery, and then continue the medication for at least 6 months after surgery.
In addition, we check pre-operative metabolic laboratories including calcium, vitamin D, and parathyroid hormone (PTH). We order calcium and vitamin D supplementation if patients have low serum levels. Physical activity, smoking cessation, and clear communication with patients are also essential parts of preparing our deformity patients for spinal fusion surgery.
We encourage others to consider similar steps for preoperative bone optimization as part of an enhanced recovery after surgery (ERAS) protocol at their own institutions. ERAS protocols are multimodal perioperative care pathways designed to achieve early recovery after surgery by maintaining preoperative organ function and reducing the profound stress of the post-operative state.34 They have been implemented successfully in many areas of surgery.34-37
Osteoporosis is increasingly common and associated with worse outcomes in spinal surgery. Patients with osteoporosis are more likely to experience fractures and surgical complications, particularly hardware-related complications including junctional kyphosis and screw pull-out. It is of utmost importance that spine surgeons are able to identify high-risk osteoporotic patients so they can optimize their bone health pre-operatively with multimodal protocols that incorporate pharmacological as well as non-pharmacological therapies.
- Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520-2526.
- Chin DK, Park JY, Yoon YS, et al. Prevalence of osteoporosis in patients requiring spine surgery: incidence and significance of osteoporosis in spine disease. Osteoporos Int. 2007;18(9):1219-1224.
- Yagi M, King AB, Boachie-Adjei O. Characterization of osteopenia/osteoporosis in adult scoliosis: does bone density affect surgical outcome? Spine (Phila Pa 1976). 2011;36(20):1652-1657.
- DeWald CJ, Stanley T. Instrumentation-related complications of multilevel fusions for adult spinal deformity patients over age 65: surgical considerations and treatment options in patients with poor bone quality. Spine (Phila Pa 1976).2006;31(19 Suppl):S144-151.
- Rollinghoff M, Zarghooni K, Groos D, Siewe J, Eysel P, Sobottke R. Multilevel spinal fusion in the aged: not a panacea. Acta Orthop Belg.2011;77(1):97-102.
- Guzman JZ, Feldman ZM, McAnany S, Hecht AC, Qureshi SA, Cho SK. Osteoporosis in cervical spine surgery. Spine (Phila Pa 1976).2016;41(8):662-668.
- Leali PT, Muresu F, Melis A, Ruggiu A, Zachos A, Doria C. Skeletal fragility definition. Clin Cases Miner Bone Metab. 2011;8(2):11-13.
- Organization WH. WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level. Summary Meeting Report.May 2004.
- Watts NB, Manson JE. Osteoporosis and fracture risk evaluation and management: shared decision making in clinical practice. JAMA.2017;317(3):253-254.
- Dipaola CP, Bible JE, Biswas D, Dipaola M, Grauer JN, Rechtine GR. Survey of spine surgeons on attitudes regarding osteoporosis and osteomalacia screening and treatment for fractures, fusion surgery, and pseudoarthrosis. Spine J.2009;9(7):537-544.
- Nyman MT, Gao T, Lindholm TC, Lindholm TS. Healing of a tibial double osteotomy is modified by clodronate administration. Arch Orthop Trauma Surg.1996;115(2):111-114.
- Nyman MT, Paavolainen P, Lindholm TS. Clodronate increases the calcium content in fracture callus. An experimental study in rats. Arch Orthop Trauma Surg.1993;112(5):228-231.
- Lenehan TM, Balligand M, Nunamaker DM, Wood FE, Jr. Effect of EHDP on fracture healing in dogs. J Orthop Res.1985;3(4):499-507.
- Amanat N, Brown R, Bilston LE, Little DG. A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair. J Orthop Res.2005;23(5):1029-1034.
- Peter CP, Cook WO, Nunamaker DM, Provost MT, Seedor JG, Rodan GA. Effect of alendronate on fracture healing and bone remodeling in dogs. J Orthop Res.1996;14(1):74-79.
- Tarvainen R, Olkkonen H, Nevalainen T, Hyvonen P, Arnala I, Alhava E. Effect of clodronate on fracture healing in denervated rats. Bone. 1994;15(6):701-705.
- Li C, Mori S, Li J, et al. Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats. J Bone Miner Res. 2001;16(3):429-436.
- Xue D, Li F, Chen G, Yan S, Pan Z. Do bisphosphonates affect bone healing? A meta-analysis of randomized controlled trials. J Orthop Surg Res.2014;9:45.
- Sugiura T, Kashii M, Matsuo Y, et al. Intermittent administration of teriparatide enhances graft bone healing and accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis. Spine J.2015;15(2):298-306.
- Qiu Z, Wei L, Liu J, et al. Effect of intermittent PTH (1-34) on posterolateral spinal fusion with iliac crest bone graft in an ovariectomized rat model. Osteoporos Int. 2013;24(10):2693-2700.
- Ming N, Cheng JT, Rui YF, et al. Dose-dependent enhancement of spinal fusion in rats with teriparatide (PTH[1-34]). Spine (Phila Pa 1976).2012;37(15):1275-1282.
- Lehman RA, Jr., Dmitriev AE, Cardoso MJ, et al. Effect of teriparatide [rhPTH(1,34)] and calcitonin on intertransverse process fusion in a rabbit model. Spine (Phila Pa 1976). 2010;35(2):146-152.
- O’Loughlin PF, Cunningham ME, Bukata SV, et al. Parathyroid hormone (1-34) augments spinal fusion, fusion mass volume, and fusion mass quality in a rabbit spinal fusion model. Spine (Phila Pa 1976). 2009;34(2):121-130.
- Abe Y, Takahata M, Ito M, Irie K, Abumi K, Minami A. Enhancement of graft bone healing by intermittent administration of human parathyroid hormone (1-34) in a rat spinal arthrodesis model. Bone. 2007;41(5):775-785.
- Lawrence JP, Ennis F, White AP, et al. Effect of daily parathyroid hormone (1-34) on lumbar fusion in a rat model. Spine J. 2006;6(4):385-390.
- Chaudhary N, Lee JS, Wu JY, Tharin S. Evidence for use of teriparatide in spinal fusion surgery in osteoporotic patients. World Neurosurg. 2017;100:551-556. Epub 2016.
- Ohtori S, Inoue G, Orita S, et al. Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis: prospective study. Spine (Phila Pa 1976). 2012;37(23):E1464-1468.
- Ohtori S, Inoue G, Orita S, et al. Comparison of teriparatide and bisphosphonate treatment to reduce pedicle screw loosening after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective. Spine (Phila Pa 1976). 2013;38(8):E487-492.
- Ohtori S, Orita S, Yamauchi K, et al. More than 6 months of teriparatide treatment was more effective for bone union than shorter treatment following lumbar posterolateral fusion surgery. Asian Spine J. 2015;9(4):573-580.
- Inoue G, Ueno M, Nakazawa T, et al. Teriparatide increases the insertional torque of pedicle screws during fusion surgery in patients with postmenopausal osteoporosis. J Neurosurg Spine. 2014;21(3):425-431.
- Seki S, Hirano N, Kawaguchi Y, et al. Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis. Eur Spine J. 2017;26(8):2121-2127. Epub 2017.
- Cho PG, Ji GY, Shin DA, Ha Y, Yoon DH, Kim KN. An effect comparison of teriparatide and bisphosphonate on posterior lumbar interbody fusion in patients with osteoporosis: a prospective cohort study and preliminary data. Eur Spine J. 2017;26(3):691-697. Epub 2015.
- American Orthopedic Association. Own the Bone. http://www.ownthebone.org. Accessed February 25, 2017.
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- Lassen K, Soop M, Nygren J, et al. Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Arch Surg. 2009;144(10):961-969.
- Wind J, Polle SW, Fung Kon Jin PH, et al. Systematic review of enhanced recovery programmes in colonic surgery. Br J Surg. 2006;93(7):800-809.