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Antiresorptive and Anabolic Medications Used in the Perioperative Period of Patients with Osteoporosis Undergoing Spine Surgery

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Antiresorptive and Anabolic Medications Used in the Perioperative Period of Patients with Osteoporosis Undergoing Spine Surgery NEUROSURGICAL FOCUS Neurosurg Focus 50 (6):E13, 2021 Antiresorptive and anabolic medications used in the perioperative period of patients with osteoporosis undergoing spine surgery: their impact on the biology of fusion and systematic review of the literature Jean-Paul Bryant, MSc, Roberto J. Perez-Roman, MD, S. Shelby Burks, MD, and Michael Y. Wang, MD Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida OBJECTIVE Osteoporosis represents the most common metabolic disease of the bone, with an estimated 10% of adults aged 50 years or older affected in the United States. This patient population is at increased risk for spine fracture and instrumentation-related complications after spine surgery. Surgeon knowledge of the available treatments for patients with low bone mineral density (BMD) and how they impact biology of fusion may help mitigate negative effects in the postoperative period. Recombinant parathyroid hormone, which is sold under the name teriparatide, is the most extensively studied bone-protecting agent in humans. Additionally, the success of the monoclonal antibody denosumab has led to further clinical investigations of human patients undergoing spine surgery. Another monoclonal antibody, romosozumab, was recently approved by the US FDA for human use in patients with osteoporosis. Although studies of romosozumab in patients undergoing spine surgery have not been conducted, this is a promising potential therapeutic agent based on its early success in preclinical and clinical trials. Here, the authors aimed to review the mechanisms of action and evidence of use of antiresorptive and anabolic agents in patients with osteoporosis undergoing spine surgery. METHODS In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted to explore the antiresorptive and anabolic agents used in the periopera- tive period in patients with osteoporosis undergoing spinal surgery. The search was performed by using the PubMed, Embase, and Cochrane Library databases. Titles and abstracts were screened and subsequently selected for full review. RESULTS The initial search returned 330 articles. Of these articles, 23 final articles were included and reviewed. Many of these articles reported that use of adjuvant agents in the perioperative period improved radiographic evidence of bony fusion and bone fusion rates. These agents tended to improve BMD postoperatively. CONCLUSIONS Although antiosteoporosis agents are effective to varying degrees as treatments of patients with low BMD, teriparatide and bisphosphonates have been the most extensively studied with respect to spinal instrumentation. The advent of newer agents represents an area for further exploration, especially due to the current paucity of controlled investigations. It is imperative for spine surgeons to understand the mechanisms of action of these drugs and their ef- fects on biology of fusion. https://thejns.org/doi/abs/10.3171/2021.3.FOCUS201049 KEYWORDS osteoporosis; spine surgery; fusion; antiresorptive; anabolic STEOPOROSIS is the most common metabolic bone women, 4%–6% of men older than 50 years also have disease, with an estimated 10.3% of adults aged osteoporosis, with another 33%–47% developing osteope- 50 years or older affected in the United States.1,2 nia.3–6 The predisposition to fracture in people with osteo- OAs the US population continues to age, the incidence of porosis has been well delineated, with 1 in 2 women older disease and complications due to osteoporosis has steadi- than 50 years and 1 in 3 men older than 70 years affected ly increased. Although osteoporosis is more common in by low-trauma fractures.7 Reports have cited as many as ABBREVIATIONS ATP = adenosine triphosphate; BMD = bone mineral density; ODI = Oswestry Disability Index; OPG = osteoprotegerin; PLIF = posterior lumbar inter- body fusion; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTH = parathyroid hormone; RANK = receptor of RANKL; RANKL = receptor activator of nuclear factor kappa B ligand. SUBMITTED December 7, 2020. ACCEPTED March 24, 2021. INCLUDE WHEN CITING DOI: 10.3171/2021.3.FOCUS201049. ©AANS 2021, except where prohibited by US copyright law Neurosurg Focus Volume 50 • June 2021 1 Unauthenticated | Downloaded 09/29/21 07:27 PM UTC Bryant et al. FIG. 1. PRISMA flowchart showing the search and review process used to select articles for this systematic review. 700,000 osteoporotic spine fractures per year, with post- anabolic agents used in the perioperative period in patients menopausal white females at the greatest lifetime risk for with osteoporosis undergoing spinal fusion. vertebral fracture.8 Those afflicted with osteoporosis present with unique Methods challenges when undergoing spinal surgery. Instrumenta- tion failure is a commonly cited complication of patients A systematic review was conducted according to the with osteoporosis who have undergone surgical interven- Preferred Reporting Items for Systematic Reviews and tion, with studies showing that decreased bone mineral Meta-Analyses (PRISMA) guidelines to investigate the density (BMD) reduces the effectiveness of pedicle fixa- use of antiresorptive and anabolic agents in spine surgery tion strength, increases the incidence of cage subsidence, patients with osteoporosis (Fig. 1). We used the PubMed and increases the risk of iatrogenic fracture and proximal MEDLINE (National Library of Medicine), Embase (El- junctional kyphosis.9–15 Placement of spinal column instru- sevier), and Cochrane Library (Wiley) databases to con- mentation in someone with low or decreased BMD often duct the search. The search terms used for each database mandates the use of special strategies, including iliac fixa- are listed in Table 1. tion techniques, extension of fixation points, and cement Duplicates were excluded after completion of the augmentation, as well as acceptance of a more modest search. The titles and abstracts of the remaining articles correction.8 Despite these technical strategies, the risk of were screened. These remaining articles were subse- complications from spine surgery remains high in patients quently screened for final review on the basis of the fol- with poor bone stock. This has elicited a need for improved lowing inclusion criteria: the study was a peer-reviewed medical therapy in the perioperative period. Numerous and full-length article; the full-length text was available drugs have been shown to be efficacious for reducing me- in English; the study included patients with osteoporosis chanical complications, and patients have demonstrated (or, in the setting of a preclinical investigation, involved an improvement in bone microarchitecture.16–21 These medi- osteoporotic animal model); the study patients underwent cations are frequently prescribed in the clinical setting and a spinal surgical procedure; the study was not a review have been well described; however, few comprehensive article; and the study patients received bisphosphonates, reviews that also include recently discovered therapeutic romosozumab, denosumab, or teriparatide. After final ex- agents exist in the spine literature. In this paper, we pres- clusion, the remaining articles were reviewed to determine ent an updated systematic review of the antiresorptive and the antiresorptive or anabolic agent administered, number 2 Neurosurg Focus Volume 50 • June 2021 Unauthenticated | Downloaded 09/29/21 07:27 PM UTC Bryant et al. TABLE 1. Search terms entered into the PubMed, Embase, and Cochrane Library databases and number of results returned No. of Results Database Search Terms Returned PubMed MEDLINE (Na- ((osteoporosis OR osteoporotic) AND (agent OR (drug)) AND (surgery OR (“spine surgery”)) AND 124 tional Library of Medicine) (spinal[TITLE] OR fusion[TITLE])) OR ((rabbit OR rat) AND fusion[TITLE] AND “parathyroid hormone”) Embase (Elsevier) (osteoporosis OR osteoporotic) AND (agent OR drugs) AND ((surgery OR “spine surgery”) AND (spinal:ti 140 OR fusion:ti) OR ((rabbit OR rat) AND fusion:ti AND “parathyroid hormone”)) Cochrane Library (Wiley) ((osteoporosis OR osteoporotic) AND (agent OR (drug)) AND (surgery OR (“spine surgery”)) AND 66 (spinal[TITLE] OR fusion[TITLE])) OR ((rabbit OR rat) AND fusion[TITLE] AND “parathyroid hormone”) of patients (or animals and species if a preclinical investi- Additionally, clinical outcomes were assessed with scores gation), surgical procedure performed, and study outcome on the visual analog scale, ODI, and 36-Item Short-Form (Tables 2 and 3). Health Survey. The mean fusion mass per level and clinical outcomes at the 6-month follow-up were similar between Results groups. This study suggests that although zoledronic acid does not decrease the volume of fusion mass, it appears to The initial search returned 330 articles (Fig. 1). Of have no clinically or statistically significant benefit com- these articles, 23 final articles were included and reviewed. pared with graft alone. Many of the final articles found that the use of adjuvant Tu et al. subsequently conducted a retrospective analy- agents in the perioperative period improved radiographic sis of 64 patients with degenerative spondylolisthesis and evidence of bony fusion. Here, we review these studies osteoporosis who underwent lumbar interbody fusion.27 on the basis of the antiresorptive or anabolic properties Half the patients (n = 32) were treated with intravenous in- of the agents used. An exhaustive
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