Pre-Operative Bone Health in Elective Spine Surgery, From Risk Assessment to Optimization Strategies: A Narrative Review

Abstract

Study Design

Narrative Review.

Objectives

Bone health optimization before spine surgery is an important but overlooked determinant of long-term postoperative outcomes. Compromised bone quality is associated with hardware loosening, pseudoarthrosis, proximal junctional failure, and revision surgery. This narrative review aims to highlight the importance of preoperative bone optimization and propose a pragmatic clinical pathway for spine surgeons. Specifically, we aimed to: (1) outline risk assessment and diagnostic strategies, including clinical risk factors, laboratory testing, and imaging such as dual-energy x-ray absorptiometry (DEXA) and opportunistic CT-based Hounsfield Unit (HU) analysis; (2) evaluate therapeutic options, emphasizing pharmacologic agents (teriparatide, romosozumab, denosumab, and bisphosphonates) alongside non-pharmacologic measures including nutrition and lifestyle modification; and (3) explore future directions, including therapy duration and economic barriers to wider adoption of newer agents.

Methods

This narrative review synthesizes the current literature on preoperative bone health management in spine surgery. Risk assessment strategies were discussed including imaging, laboratory testing, and clinical picture analysis. Therapeutic options evaluated emphasize pharmacologic agents alongside non-pharmacologic measures.

Results

Despite the clinical relevance of compromised bone quality to poor surgical outcomes, bone health assessment remains inconsistently incorporated into surgical planning. Current evidence supports a multimodal approach combining targeted assessment and timely intervention to mitigate risk of adverse bone-related events following spine surgery.

Conclusions

Preoperative bone health optimization is a crucial opportunity to improve long-term outcomes for patients undergoing spine surgery. Adoption of a standardized clinical pathway for risk stratification, diagnosis, and treatment may provide a valuable framework for improving fixation stability and fusion rates.

Introduction

Bone health has emerged as a growing priority in the United States as the population continues to age. According to the Surgeon General’s report on bone health and osteoporosis, osteoporosis-related complications cost the U.S. roughly $12 to 18 billion annually. Of this population, approximately 1.5 million osteoporotic fractures led to more than half a million hospitalizations in the same year. ¹ The CDC also reports an increase in risk for osteoporosis in Americans over 50 years old growing from 9.4% in 2007-2008 to 12.6% in 2017-2018. ²

The terms osteopenia and osteoporosis help physicians describe bone mineral density (BMD) values lower than normal reference values. Osteopenia is defined by the World Health Organization (WHO) as a T-score between −1 to −2.5, while osteoporosis is characterized by a T-score of less than −2.5.^3,4 This score quantifies diminished bone mass and microarchitectural disruption of both trabecular and cortical bone. ⁵ The T-score is typically calculated using dual-energy x-ray absorptiometry (DEXA) bone scans of the hip or lumbar spine. The resulting calculated BMD score is then compared with the mean BMD score of healthy young population in terms of the number of standard deviations, reported as a T-score.^5-7 Another qualification for a diagnosis of osteoporosis is the presence of fragility fractures (e.g. hip, spine, wrist), also known as low-energy fractures that would not normally cause fracture in average healthy persons. ⁸

Nearly 50% of postmenopausal women will have an osteoporotic related fracture in their lifetime. ³ In this population, a low BMD and prior fracture are associated with increased risk of fracture in the next 10 years.^9,10 Additionally, it has been suggested that all regions of the spine were placed at increased risk by the presence of prevalent fractures (Odds ratio [OR] 2-5 for developing incident fractures outside the prevalent region). The mechanism supporting this is hypothesized that prevalent fractures may initiate local mechanical or biochemical inflammatory markers during fracture healing that is able to spread to nearby and distant vertebrae. ¹¹ Furthermore, bone health is also determined by a patient’s age, family history, and use of oral corticosteroids.^12,13

Spinal surgery success is closely tied to bone integrity. In populations with osteopenia or osteoporosis, reduced bone mass compromises pedicle screw fixation, heightens risk of nonunion, and predisposes to complications such as proximal junctional failure. As such, proactive pre-operative bone health management should be integral to surgical planning. The aim of this review is to provide a framework for preoperative bone health optimization in spine surgery by: (1) outlining diagnostic strategies to identify patients at risk; (2) evaluating pharmacologic and non-pharmacologic interventions to improve bone quality; and (3) discussing ongoing challenges and future directions that influence clinical decision-making, including a sample preoperative algorithm.

Methods

A comprehensive literature search was conducted to identify relevant studies focusing on preoperative bone health optimization in elective spine surgery. The primary databases searched included PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library for articles published between 1990 and 2024. Search terms included, but were not limted to: ‘spine surgery’, ‘bone health optimization’, ‘preoperative osteoporosis’, ‘teriparatide’, ‘romosozumab’, and ‘Hounsfield units’.

The inclusion criteria were clinical trials, cohort studies, and systematic reviews published in the English language that addressed risk stratification, diagnostic imaging, and pharmacological or non-pharmacological interventions for spine surgery candidates. Reference lists of identified articles were manually screened for additional relevant sources to ensure the inclusion of high-quality evidence.

Diagnostic Assessment

Clinical Risk Assessment

It is recommended that all patients, regardless of age, should be screened/asked about bone health risk factors including:

• • History of prior fracture(s)

• • Glucocorticoid use

• • Endocrine disorders (thyroid disease, diabetes, hypogonadism, early menopause)

• • Smoking

• • Heavy alcohol use (for men ≥14 drinks/week, for women ≥7 drinks/week)

• • Family history of osteoporosis/fracture (e.g. parental history of hip fracture, distal radius fracture, and/or other fragility fracture)

Laboratory Testing

Major society guidelines, ¹⁴ including from the National Osteoporosis Foundation (NOF), International Society for Clinical Densitometry (ISCD), American Association of Clinical Endocrinology (AACE), and the Endocrine Society, include core laboratory testing for nearly all high risk patients including:

• • Serum calcium

• • Phosphate

• • Albumin

• • Renal function (serum creatinine/glomerular filtration rate [GFR])

• • Alkaline phosphatase

• • 25-hydroxyvitamin D

Calcium and phosphate are essential minerals in the body that aid in bone mineralization, intracellular signaling, and neuromuscular function. Obtaining these serum levels aids clinicians in detecting conditions causing hypercalcemia such as primary hyperparathyroidism or hypocalcemia that may result from chronic kidney disease. ¹⁵ There has been some controversy over the adequacy of using an albumin corrected serum calcium level vs total serum calcium. Approximately half of calcium found in the body is bound to albumin in the inactive state, while the other half is biologically active ionized form. A recent study demonstrated that unadjusted calcium is superior in terms of cost, however albumin adjusted calculations tend to underestimate true hypocalcemia especially in cases of low albumin. ¹⁵ This underestimation was also found in a further analysis of critically ill patients, kidney failure on dialysis, and geriatric patients.^16-18

The interplay between renal function and bone density has been well studied in recent literature. Primary markers of serum creatinine and GFR provide helpful markers in detecting renal disease which can negatively affect bone health. It has been reported that approximately 20% of the U.S. over 65 years old has chronic kidney disease stage ≥3, and patients with end-stage renal disease are at an increased risk for osteopenia and fracture.^19,20 The pathophysiology behind this notes that a GFR below 60 mL/min/1.73 m², indicating chronic renal failure, leads to a retention of phosphate at the proximal convoluted tubule opposing the normal function of the kidney to excrete phosphate. This increase in serum phosphate will then bind to calcium in the blood, leading to a serendipitous decrease in serum calcium. In response to a low serum calcium, the parathyroid increases PTH and decreases serum 1,25-dihydroxyvitamin D levels, both of which negatively affect bone density. ²¹ In addition to GFR, serum creatinine provides a useful insight into kidney function. Creatinine is a product of muscle breakdown and a useful surrogate marker for muscle mass, however a high serum creatinine can also indicate decreased kidney filtration and thus should be included in a laboratory panel. ²⁰

While serum alkaline phosphate (ALP) is not sensitive enough to detect bone remodeling in osteoporotic bone, it does provide useful insight into the detection of Paget’s disease, metastatic bone disease, and osteomalacia. An elevated ALP may also be due to liver disease, in which case gamma-glutamyl transpeptidase (GGT) should be utilized instead. ²²

Additional laboratory testing to consider based on risk factors/history^14,22 include:

• • TSH, free T4 – hyperthyroidism

• • Testosterone (in men) – hypogonadism

• • HbA1c or fasting glucose

• • 24-hr urine calcium

• • Serum protein electrophoresis (SPEP/UPEP)

• • Celiac serologies (tTG IgA) if history suggests malabsorption

Thyroid function also plays an important role in bone heath. Recent data suggests that both hypothyroidism and hyperthyroidism can contribute to a low bone mineral density (BMD) and thus increased risk of fracture. ²³ Similarly hyperparathyroidism may affect bone integrity and testing for PTH should also be included in a bone health panel.

Sex hormones including estrogens and androgens have been well studied in the literature in relation to bone health. Androgens such as testosterone found in both men and women aid in periosteal growth through osteoblast stimulation and osteoclast suppression.^24-26 Because men have more testosterone, they also have greater cortical thickness and peak bone mass than women. ²⁷ Age-related bone loss in men can also be due to estradiol deficiency if not enough testosterone is aromatized to estradiol. ²⁸ Alternatively estrogens help maintain cortical and cancellous bone through increased osteoprotegerin production leading to inhibition of osteoclast differentiation. ²⁷ Therefore, when estrogen is decreased in menopause in women, there is a decrease in bone density. This relationship is borne out by the fact that 1/3 of females over 50 years old have an increased risk of osteoporotic fractures in comparison to 1/5 of men.^29,30

Current recommendations for lab values in testing for osteoporosis are summarized in Table 1. In accordance with the U.S. Preventative Services Task Force (USPSTF), we recommend screening for osteoporosis start in all postmenopausal women, women over 65 years old, and men over 70 years old. ³¹ Osteoporosis screening should also be considered in people with a high risk of fragility fracture as well as in those with underlying conditions that predispose them for bone loss such as renal failure. While most elements of laboratory screening for osteoporosis are included on standard outpatient laboratory testing, we encourage further testing of secondary causes if there a high degree of clinical suspicion.

Table 1.

Recommended Laboratory Testing for Osteoporosis

	Normal reference values:	Special indications
Primary laboratory data
Serum calcium	8.5-10.2 mg/dL	F: post-menopause or 65yo+ M: 70yo+
Serum phosphate	2.5-4.5 mg/dL
Albumin	3.5-5.5 g/dL
Alkaline phosphatase	Male: 40-129 IU/L Female: 39-115 IU/L 65+ yo: 30-130 IU/L
Creatinine	Male: 0.6-1.2 mg/dL Female: 0.5-1.1 mg/dL
Secondary laboratory data
25-Hydroxyvitamin D	50 nmol/L22
PTH	10-65 pg/mL	Serum calcium abnormalities; high degree of clinical suspicion
TSH	0.4-1.5 lU/mL
Testosterone	Adult male (18+): 264-916 ng/dL Adult female (18+): -premenopausal: 10-55 ng/dL -postmenopausal: 7-40 ng/dL
Estrogen	Male: 10-40 pg/mL Female: -premenopausal: 15-350 pg/mL -postmenopausal: <30 pg/mL

Imaging and Bone Quality Metrics

Dual x-ray Absorptiometry (DEXA)

Dual x-ray absorptiometry scores (DEXA) remain the standard of care for assessing bone mineral density (BMD). DEXA utilizes a BMD score that when compared to the average healthy, young population is expressed as the number of standard deviations from the mean and termed the T-score. A T-score between −1 to −2.5 is indicative of osteopenia, while a T-score of less than −2.5 is indicative of osteoporosis.^5-7 While BMD is useful in the diagnosis of osteoporosis and osteopenia, a low BMD score is in actuality an inefficient tool for identification of those at a high risk of fractures. Rather, it is best to use algorithms that in addition to BMD include age, sex, BMI, family history of fractures, personal fracture history, and secondary causes of osteoporosis such as chronic glucocorticoid use, excessive smoking, alcohol use, and rheumatoid arthritis.^22,32

The optimal screening frequency is not well reported in current literature, however the USPSTF guideline recommends starting screening in postmenopausal or women over 65 years old, and men over 70 years old, at intervals of a minimum of every 2 years to adequately measure a change in BMD, although this is not correlated with fracture risk prediction.^31,33 However, a large cohort prospective study of women aged 65 or older found that repeated DEXA scanning after 8 years provided no more predictive value of fracture risk than the original BMD measurement. ³⁴

Alternatively, Fracture Risk Assessment Tool (FRAX®) scoring may be utilized to predict 10 year probability of fracture. This is a free online tool that can be utilized in conjunction with DEXA scanning by clinicians. FRAX® scoring system uses an algorithm to combine patient variables such as age, sex, BMI, geographic location, BMD, and a history of various risk factors that may predispose someone to fracture. A score will be reported as % risk of fracture within 10 years. Online calculator can be found at fraxplus.org. ³⁵

Hounsfield Units (HU)

DEXA remains the clinical gold standard for diagnosing osteoporosis and predicting fracture risk. However, a major limitation to DEXA is that it may miss localized poor bone quality. Opportunistic Hounsfield Units (HU) analysis of pre-existing computed tomography (CT) scans at the planned screw trajectories preoperatively may serve as a useful adjunctive screening tool, particularly in the spine surgery population where degenerative changes can lead to falsely elevated DEXA T-scores.^36,37 HU is a quantitative measurement radiologists calculate that measures the difference in absorption/attenuation of the X-ray beam, translated to density of bone compared to density of distilled water. This provides a clearer picture in 3 dimensions compared to the 2 dimensional DEXA scan. However, there is additional risk of radiation exposure with CT vs DEXA, so HU should only be used if pre-operative imaging is available and not as a first-line screening tool. Bones can reach a maximum HU of 1000-2000 with more dense bones falling in the upper limit of this range. ³⁸ While a T-score is not calculated from CT measured HU, several studies have reported correlation of HU to T-scoring systems.^39,40 HU are typically measured using axial CT slice at mid-vertebral body, ideally excluding cortical bone, venous plexus and/or sclerotic changes. Of note, there are differences in the cutoff of HU between spine levels that need to be considered.

The cervical spine has significantly greater bone density in comparison to lumbar vertebrae as it contains a substantially higher trabecular bone network. When comparing HU values at each level of the spine it is important to consider demographic variables such as racial and ethnic disparities in determining cutoff HU values as these are known to affect bone health and outcomes. For example, it is known that non-Hispanic Black women and Mexican American women have significantly higher BMDs than non-Hispanic White women. Additionally, BMDs in Chinese and South Asian populations are significantly lower than Caucasians. ⁴¹ A study from Korea reported a cervical HU cutoff of 284 for a diagnosis of osteopenia and 231.5 for osteoporosis. ³⁹ Alternatively, a study done in Bronx, New York including a much more diverse population reported a HU cutoff of 340.98 for osteopenia and 326.5 for osteoporosis. ⁴⁰ The wide range in HU scoring cutoffs highlights existing gaps in the literature that warrants further investigation.

The lumbar spine has also been well studied in the literature on the role of HU scoring in relation to bone health. A systematic review including 5307 patients reported an optimal HU cutoff of 78-146 for osteopenia, 54.7-130 for osteoporosis, and a normal range of 120.8-230. ⁴² Additionally, HU can be applied to prediction of pedicle screw loosening postoperatively. A retrospective study including 503 patients reported that lower HU values are independently predictive of screw loosening (Mean HU of 106 in the loosening group vs 133 in the control group; OR showing significance). ⁴³ Of note, another study reported at the lumbosacral junction, HU values along the S1 screw trajectory significantly predicted loosening risk, with HU values having the highest predictive accuracy over other factors (AUC = 0.79). ⁴⁴ Additionally, while DEXA has become a powerful predictor of bone degradation, it is most accurate in the lumbar spine and proximal femur, and inaccurate in patients with lumbar scoliosis or degenerative changes.^45,46

Finally, the thoracic spine is the most under-studied level of the spine and is often sub-categorized into upper (T1-T4) and lower (T9-T12) vertebrae due to the wide range of bone density from cranial to caudal thoracic spine. A retrospective study from Seol reported a HU cutoff for both upper and lower vertebrae of 126.3 predicted screw loosening better than T-scores. They noted lower HU levels were associated with higher rates of screw loosening at the lower thoracic levels, but not the upper thoracic levels. ⁴⁷ A retrospective study of the thoracolumbar spine reported that in T11 a HU score of <105.1 and in T12 a HU score of <85.7 were indicative of osteoporosis. ⁴⁸ However, another retrospective study at a single hospital with 1112 patients compared HU cutoffs for osteoporosis of T11-T12 < 125 HU vs L1-L2 HUC<107 and found no significant difference between the groups. ⁴⁹ This allows for generalization of osteoporotic risk between thoracolumbar regions in future assessments. In the upper thoracic vertebrae (T1-T6) another retrospective study reported proximal junctional failure rates of 59% at HU<147, 33% at HU 147-195, and 7% at HU>195. ⁵⁰

Hounsfield Units Better Marker for Local Bone Quality

When planning spine surgery, Hounsfield Unit (HU) values from the vertebrae are often more informative than bone density measurements from other skeletal sites (Figure 1). Hip DEXA can underestimate or overestimate the true quality of spinal bone, since it does not always reflect the condition of the vertebrae themselves. It is not unusual to see patients with hip osteoporosis who maintain relatively preserved bone in the spine, or the opposite scenario where the hips appear normal but the vertebrae are markedly osteoporotic. Because HU is measured directly at the surgical levels, it offers surgeons a site-specific assessment that better predicts fixation strength and risk of instrumentation failure. Table 2 summarizes the general cutoff recommendations with DEXA and HU for diagnosis of osteopenia vs osteoporosis.

Figure 1.

Representative Images demonstrating Hounsfield Unit Measurements for Normal/Osteoporotic Cervical/Thoracic/Lumbar Spine. (A) Normal Cervical (B) Normal Thoracic (C) Normal Lumbar (D) Osteoporotic Cervical (E) Osteoporotic Thoracic (F) Osteoporotic Lumbar

Table 2.

Recommended Imaging Cutoffs for Diagnosis of Osteoporosis

DEXA5-7
Normal T-score	> −1
Osteopenia T-score	−1 to −2.5
Osteoporosis T-score	< −2.5
Indications	F: post-menopause or 65yo+ M: 70yo+
HU
Cervical	-Normal: >300-325 HU -Osteopenia: ∼250-325 HU -Osteoporosis <250 -Red flag for surgery: <200
Thoracic	-Normal: >175-200 -Osteopenia: 135-175 -Osteoporosis: <135 -Red flag for surgery: <100
Lumbar	-Normal: >135-150 -Osteopenia: 110-135 -Osteoporosis: <110 -Red flag for surgery: <90

Note: HU values are subject to significant variability based on scanner settings and software. These values represent a synthesis of common published thresholds and should be used as adjunctive screening tools rather than standalone diagnostic substitutes.

HU Limitations

While HU analysis offers the advantage of a more sensitive evaluation of trabecular bone quality without additional radiation or cost, it possesses significant limitations. Unlike DEXA, HU measurements lack universal standardization; values can vary significantly based on CT scanner manufacturer, tube voltage (kVp), the presence of intravenous contrast, and whether the measurements are performed on axial or sagittal reconstructions. Consequently, a single gold standard HU cutoff has not been established. Furthermore, there is no globally accepted HU threshold for osteoporosis that matches the diagnostic precision of a DEXA T-score. Additionally, the literature remains limited in establishing optimal cutoff values for disease diagnosis due to wide variability in bone density across the length of the spine. Consequently HU should be interpreted as a screening metric that warrants further clinical correlation rather than a standalone diagnostic substitute. Further investigation is warranted on this topic to guide more accurate diagnosis algorithms.

Pharmacologic Management

Anti-Resorptive Therapies

Bisphosphonates were among the earliest drugs introduced for the preservation of bone mass, with etidronate becoming available in the 1970s and alendronate following in the 1990s. ⁵¹ These agents act by binding to hydroxyapatite crystals in bone, which suppresses osteoclast-mediated resorption and slows bone turnover. ⁵² Their fracture prevention benefits have been confirmed in multiple large randomized controlled trials, establishing bisphosphonates as a central therapy in osteoporosis management. ⁵³ Alendronate reduces vertebral fracture risk by approximately 50% and decreases hip and other nonvertebral fractures by about 30%. ⁵⁴ Risendronate lowers vertebral and nonvertebral fractures by roughly 40%, while ibandronate demonstrates about a 50% reduction in vertebral fractures but no significant effect on nonvertebral fractures. ⁵⁴ Zoledronic acid shows the strongest efficacy, with up to a 70% reduction in vertebral fracture risk. ⁵⁵

Long-term treatment outcomes and the role of “drug holidays” remain areas of ongoing discussion. Maximal therapeutic effect is typically achieved within 3-6 months, and clinical practice often recommends use for 3-4 years; however, emerging evidence suggests benefits can extend up to 10 years with continue therapy.^56,57 The Fracture Intervention Trial Long-term Extension (FLEX) trial highlighted these findings: women who stopped alendronate after five years experienced a moderate decline in lumbar spine bone mineral density over the following decade (−3.7%), whereas those who continued therapy maintained significantly lower rates of vertebral fractures (2.4% vs 5.3% with placebo). Importantly, this protective effect was not observed for nonvertebral fractures. ⁵⁸ In practice, dosing regimens vary by agent: alendronate (35 mg weekly for prevention; 70 weekly for treatment), risendronate (35 mg weekly or 150 mg monthly), ibandronate (150 mg orally once monthly or 3 mg IV monthly), and zolendric acid (4-5 mg IV annually). Patients should also receive calcium (1000-1200 mg/day) and vitamin D (800-1000 IU/day) if dietary intake is insufficient. ⁵⁹ Of note, adverse effects of bisphosphonates include esophageal irritation, flu-like symptoms, osteonecrosis of the jaw, and are contraindicated in severe renal impairment. Beyond efficacy, bisphosphonates remain a cost-effective option compared with newer anabolic and monoclonal antibody therapies, making them highly relevant for bone health optimization in patients undergoing spine surgery. ⁶⁰

Denosumab

Denosumab is a newer anti-resorptive agent approved in 2010 for treatment of postmenopausal osteoporosis and other bone-related disorders. Its mechanism is distinct from bisphosphonates, as it inhibits the receptor activator of nuclear factor-κB ligand (RANKL), thereby preventing osteoclast activation and reducing bone resorption. ⁶¹ Unlike bisphosphonates, which eventually reach a plateau in their effects, denosumab has been shown to produce progressive increases in lumbar spine bone mineral density (BMD) over time. ⁶² Comparative studies demonstrate superior gains in BMD with denosumab; for example, a retrospective analysis in 2017 reported greater lumbar spine BMD improvements in patients treated with three years of denosumab compared to those who had long-term bisphosphonate therapy followed by denosumab (12.9% vs 7.5%). ⁶³ In the spine surgery setting, its impact has been evaluated in a two-year prospective study utilizing finite element analysis, which found significant increases in BMD at 12 and 24 months in patients treated with denosumab before undergoing pedicle screw fixation. ⁶⁴ These findings underscore its potential not only for fracture prevention but also for improving surgical fixation outcomes, making it a key agent in preoperative bone health optimization.

Denosumab is administered as a 60 mg subcutaneous injection every six months, typically in the upper arm, thigh, or abdomen. Patients should receive adequate calcium supplementation (approximately 1000 mg daily) along with at least 400 IU of vitamin D if dietary intake is insufficient, and a BMD should be reassessed with DEXA scanning every two years while on therapy. ⁶⁵ A major clinical concern is the rebound effect observed upon discontinuation: withdrawal of denosumab is associated with rapid bone loss, elevated bone turnover makers, and an estimated 20% risk of multiple vertebral fractures in postmenopausal women. ⁶⁶ To mitigate this, transition therapy with a potent bisphosphonate such as alendronate or zoledronic acid is recommended, although high doses may carry risk of renal impairment. ⁶⁵ Additional adverse effects include back and extremity pain, hypercholesterolemia, osteonecrosis of the jaw, and atypical femoral fractures with long-term use. Despite this limitation, denosumab’s sustained efficacy in increasing BMD and its ability to enhance spinal instrumentation stability make it an important tool in optimizing bone health prior to surgery.

Teriparatide

Teriparatide, a recombinant analogue of parathyroid hormone (PTH 1-24), classified as an anabolic agent that promotes new bone formation through stimulation of osteoblast activity. Alongside abaloparatide, it represents a primary therapeutic option for patients with severe osteoporosis. Although continuous elevations of PTH, as seen in primary hyperparathyroidism, cause bone loss, it has been established that intermittent administration of teriparatide exerts anabolic effects on the skeleton.^67,68 Evidence from the pivotal Fracture Prevention Trial (Neer et al., 2010) demonstrated that daily subcutaneous injections of 20 μg reduced the risk of new vertebral fractures by 65% and nonvertebral fragility fractures by 53%, while increasing lumbar spine BMD by 9% and femoral neck BMD by 3% over a median follow-up of 21 months. ⁶⁹ These findings established teriparatide as an effective bone-forming therapy and laid the groundwork for its potential use in spine surgery.

In the surgical setting, teriparatide has been associated with superior outcomes compared to antiresorptive therapies.^70,71 A systematic review of 676 spinal surgery patients found teriparatide significantly improved fusion rates relative to bisphosphonates. ⁷¹ Similarly, a 2012 prospective trial of women undergoing decompression and instrumented fusion showed higher fusion rates (82% vs 68%) and faster union times (8 vs 10 months) in those receiving teriparatide. ⁷² Longer treatment duration appears to provide additional benefit: a 2017 retrospective study reported that courses of at least six months were associated with a greater proportion of patients achieving solid fusion (66.7% vs 50%). ⁷³ Meta-analyses also confirm that teriparatide enhances fusion, reduces screw loosening, and improves HU-based BMD, though functional scores remain unchanged. ⁷⁴ However, recent data highlight anatomic considerations; a 2025 retrospective cohort of cervical spine patients with osteopenia found higher implant failure (4.1% vs 1.0%) and revision rates (54.1% vs 4.7%) among teriparatide-treated patients compared to matched controls, suggesting biomechanical differences between cervical and lumbar constructs may alter therapeutic efficacy. ⁷⁵ The mechanism for this site-specific disparity is not fully understood but may relate to the unique biomechanical environment of the cervical spine. Taken together, teriparatide offers robust evidence for improving bone quality, fusion and instrumentation in the lumbar spine. However, surgeons should exercise caution when prescribing teriparatide for cervical procedures and consider alternative antiresorptive or anabolic agents until more definitive prospective data are available. Additional common adverse effects include nausea, dizziness, leg cramps, and transient hypercalcemia.

Romosozumab

Romosozumab is a newer anabolic therapy that functions as a humanized monoclonal antibody and sclerostin inhibitor, approved by the FDA in 2019 for postmenopausal osteoporosis. ⁷⁶ By blocking sclerostin, it simultaneously stimulates bone formation and suppresses bone resorption through the Wnt signaling pathway. ⁷⁷ This was further supported by a Phase 2 trial of 419 postmenopausal women followed over one year, which demonstrated that 210 mg of romosozumab administered monthly increased lumbar spine BMD by 11.3%, compared with 4.1% with alendronate and 7.1% with teriparatide (P < .001). ⁷⁸ More recent data also suggests its superiority in surgical populations: a 2024 retrospective study of spine and non-spine surgery patients found that romosozumab treatment yielded a 26% improvement in vertebral Hounsfield Units (HU) over 10.5 months, outperforming teriparatide’s 25% gain achieved over 23 months, while little change was observed in patients treated with denosumab or alendronate. ⁷⁹ Confirming these results, a systematic review of four randomized control trials proved romosuzumab to have both better efficacy, as indicated by a T-score of −2.0 or less at the lumbar spine, and improved side effect profile when compared with teriparatide. ⁸⁰ These findings highlight romosozumab’s rapid and robust effects on bone quality, with greater efficacy than existing anabolic agents.

While romosozumab holds promise for preoperative bone health optimization in spine surgery, safety concerns must be considered. A large double-blind randomized controlled trial of more than 4000 postmenopausal women reported a higher rate of serious cardiovascular adverse events in patients receiving romosozumab compared with alendronate (2.5% vs 1.9%). ⁸¹ It has been hypothesized that sclerostin may play a cardioprotective role, and that patients with pre-existing conditions such as diabetes, chronic kidney disease, or prior cardiovascular disease may be at higher risk. ⁸² Because of this, romosozumab carries a “black box” warning regarding the risk of myocardial infarction, stroke, and cardiovascular death. Additionally, cost remains a significant barrier to the widespread adoption of newer anabolic agents such as romosozumab and teriparatide, compared with bisphosphonates or denosumab. The high upfront cost of a 12-month course of romosozumab may be offset by the avoidance of surgical complications such as pseudoarthrosis or proximal junctional kyphosis, which often require expensive revision procedures. However, these high costs may not be feasible for every patient to supply up front in which case other agents should be considered.

Taken together, romosozumab offers rapid and substantial improvements in BMD and may enhance fusion and fixation outcomes in spine surgery, but its use should be individualized, particularly in patients with elevated cardiovascular risk.

Selective Estrogen Receptor Modulators (SERMs)

Selective Estrogen Receptor Modulators (SERMs) such as tamoxifen and raloxifene work as estrogen receptor agonists or antagonists depending on target tissue in the body and are commonly used in both breast cancer and osteoporosis. ⁸³ Estrogen has a critical role in bone metabolism by binding to receptors on osteoblasts, osteoclasts, and osteocytes, leading to decreased production and lifespan of osteoclasts while stimulating osteoblast activity. Loss of estrogen, particularly in postmenopausal women, reduces osteoblast lifespan and shifts bone remodeling toward increased resorption and decreased formation, ultimately resulting in bone loss. ⁸⁴ SERMs aim in osteoporotic patients is to counteract this negative balance by mimicking estrogen’s protective effects on bone without stimulating estrogen-sensitive tissues such as the uterine endometrium. Tamoxifen, a triphenylethylene derivative, while valuable in breast cancer treatment, has more complex effects on bone depending on menopausal status and is not considered a first-line therapy for osteoporosis.^85,86

Raloxifene, a benzothiophene derivative, is widely studied and approved for postmenopausal osteoporosis at a daily dose of 60 mg. In a large, multicenter, randomized, placebo-controlled trial of 7705 women, raloxifene demonstrated significant increase in lumbar spine bone mineral density (2.6-2.7%, P < 0.001) and reduced vertebral fracture risk. ⁸⁷ More recently, lasofoxifene, a third-generation SERM and naphthalene derivative, has shown improved skeletal efficacy compared to raloxifene at an oral dose of 0.5 mg/day, demonstrating benefits in both vertebral and nonvertebral fracture prevention in postmenopausal women. ⁸⁸ While hot flashes and an increased risk of venous thromboembolism remain notable adverse effects, SERMs represent an important pharmacologic option for spine surgery patients with poor bone quality, particularly when optimizing bone health preoperatively.

Calcitonin

Calcitonin, a peptide hormone secreted by parafollicular cells of the thyroid gland, has been adapted into therapeutic formulations such as salmon calcitonin for the treatment of postmenopausal osteoporosis, Paget disease, and hypercalcemia. Its primary mechanism of action involves suppression of osteoclast activity, which reduces bone resorption, along with enhanced renal clearance of calcium. ⁸⁹ Because of its modest impact on bone health, calcitonin is generally reserved for postmenopausal women who are at least five years beyond the onset of menopause. ⁹⁰ In the context of spine surgery, its potential role lies in improving skeletal stability through decreased bone turnover, though its overall use has declined with the advent of more potent antiresorptive agents. ⁹¹

Clinical studies have demonstrated that calcitonin can reduce vertebral fracture risk, though its efficacy is not as strong as other available therapies. The pivotal 5-year “PROOF” trial, which enrolled 1108 postmenopausal women, showed that a daily intranasal dose of 200 IU reduced new vertebral fractures by 33% and led to a modest increase in lumbar spine bone mineral density (1-1.5% above baseline). However, no significant benefits were observed for hip and other non-vertebral fracture prevention in this study. ⁹² Recommended dosing strategies include 200 IU intranasally once daily or 100 IU administered via subcutaneous or intramuscular injection, with concurrent calcium and vitamin D supplementation to optimize outcomes. ⁹³ Despite being less effective than bisphosphonates in terms of BMD improvement and fracture prevention, calcitonin may still serve as an adjunct in select cases of bone health optimization before spine surgery. Table 3 outlines the important considerations and dosing recommendations of the aforementioned common medications utilized in bone health management.

Table 3.

Recommended Dosing of Common Pharmacologic Management

Drug class	Recommended dosing	Important considerations
Bisphosphonates	Alendronate: 35 mg PO weekly for prevention, or 70 mg PO weekly for treatment Risendronate: 35 mg PO weekly or 150 mg PO monthly Ibandronate: 150 mg PO once monthly or 3 mg IV monthly Zolendric acid: 4-5 mg IV annually	Need for “drug holidays” Calcium and vitamin D supplementation
Denosumab	60 mg SQ every six months	Calcium and vitamin D supplementation Caution: Rebound effect may increase risk of fracture
Teriparatide	20 μg SQ daily	Caution in cervical spine disorders
Romosozumab	210 mg SQ once monthly	May increase risk for cardiovascular events
Selective Estrogen Receptor Modulators (SERMs)	Raloxifene: PO 60 mg daily Lasofoxifene: PO 0.5 mg daily	Adverse events: hot flashes and increased risk of VTE
Calcitonin	200 IU intranasally daily 100 IU SQ or IM daily	Calcium and vitamin D supplementation

Non-Pharmacologic Optimization

Nutrition/Supplements

Nutritional optimization plays an important role in the preventative measures of osteoporosis and is generally lower cost to patient than alternative medication management. By the age of 30 most people achieve peak bone mass, so early optimization of calcium and vitamin D are imperative. The mechanism of vitamin D in bone health is well-known as it promotes calcium absorption in the gut and regulates bone remodeling. Deficiencies in vitamin D may be caused by hyperparathyroidism and are also linked to osteoporosis. ⁹⁴ To prevent these effects it is recommended to consume 700-800IU/day of vitamin D to reach a target serum 25(OH)D concentration of 75 nmol/l (Table 4). Unfortunately, this target range is believed to be achieved by only about 1/3 of US older adults. ⁹⁵ Good sources of vitamin D in the diet are in fatty fish, eggs, fortified foods, mushrooms, and liver.

Table 4.

Vitamin D Supplementation Protocol Prior to Elective Spine Surgery

25(OH)D Level	Initial Treatment	Duration	Follow-up/Maintenance	Notes
<20 ng/mL	50 000 IU vitamin D orally once weekly	2-3 months	Then ≥1000 IU/day; recheck level at 3 months	Goal: Normalize to >30 ng/mL
20-30 ng/mL	1000 IU/day	∼3 months	May require higher dose if levels remain low	Dose should be adjusted based on repeat serum 25(OH)D
Normal (>30 ng/mL)	—	—	Continue 800 IU/day for maintenance	Avoid stopping therapy or using inadequate long-term maintenance dose

It is also important to monitor calcium and protein intake to support osteogenesis and surgical healing. It has been found that the average woman over 40 years old consumes less than half of the daily recommended calcium (1000 mg) for postmenopausal women. ⁹⁶ There is controversial data currently on the role of protein in the formation of osteoporotic bone. A prospective cohort study reported an increased protein intake (>1.2 g/kg body mass/day) in postmenopausal women was negatively correlated with BMD in a 3 year follow up. This study did note that there may have been a confounding limitation in the population as most patients had an elevated BMI (>30 kg/m2). ⁹⁷ Opposing this view, a meta-analysis of placebo-controlled randomized trials reported a small positive effect of protein supplementation on lumbar spine BMD that may not translate to a reduction in fracture risk. ⁹⁸

Prehabilitation and Physical Activity

It has been well recognized in the medical community that exercise is preventative for risk of most major diseases, including osteoporosis. In women, peak bone mass is earlier than men (around 15-20 years of age) and is succeed by a rapid decline in bone remodeling in later life. This process is further complicated by the decrease in osteoprotective estrogen in postmenopausal women. ⁹⁹ A blinded randomized controlled trial of elder osteoporotic patients, both male and female, assigned to either medical management group or weight-bearing exercise group with 6 months follow up reported a statistically significant difference in T-score of the lumbar spine at the end of treatment with weight-bearing showing the greatest improvement. ¹⁰⁰ It is advisable for patients to incorporate weight-bearing, resistance, and balance exercises pre-operatively to build bone strength and reduce postoperative fall risk.

Lifestyle and Comorbidity Management

Lifestyle modification is a critical component of managing poor bone health, and should be addressed alongside pharmacologic and surgical interventions. Smoking cessation is paramount, as a meta-analysis including nearly 60 000 patients found that current smoking was associated with a significantly elevated fracture risk (RR = 1.25; 95% CI = 1.15-1.36). ¹⁰¹

Similarly, moderation of alcohol intake is essential. In a large cohort study of more than 40 000 individuals, alcohol consumption was linked to increased fracture risk at major osteoporotic sites, including the thoracic and lumbar spine, proximal humerus, distal forearm, and hip. ¹⁰²

Beyond lifestyle factors, optimizing control of comorbidities such as diabetes, thyroid dysfunction, and other metabolic disorders is equally important, as these conditions can impair bone turnover, delay healing, and compromise long-term skeletal integrity. Comprehensive patient counseling and multidisciplinary management can therefore play a pivotal role in improving surgical outcomes and sustaining bone health over time.

Referrals

Our review highlights overall strategies to optimize bone health prior to spine surgery, but it is important to recognize some patients may require separate specialty referral for further management. Individuals with metabolic bone disorders, recurrent fragility fractures, severe osteoporosis, or other causes of low bone density (e.g. endocrine abnormalities, chronic kidney disease, rheumatologic conditions) may benefit from a physician referral to an endocrinologist and/or rheumatologist.

Proposed Clinical Algorithm

The following clinical algorithm is proposed as a practical framework based on the authors’ synthesis of available evidence and current professional society guidelines. While these steps reflect the emerging best practices in preoperative bone health optimization, it is important to note that this specific pathway has not undergone formal prospective validation. It is intended to guide clinical decision-making and provide a foundation for future longitudinal studies to confirm its efficacy in improving surgical outcomes.

• 1. Screening: For osteoporosis, recommend starting screening in all postmenopausal women, women over 65 years old, and men over 70 years old. All candidates should undergo risk assessment, labs, DEXA ± opportunistic CT HU evaluation.

  •  a. Core Labs: Order serum Calcium, Phosphate, Albumin, Renal function (creatinine/glomerular filtration rate), Alkaline phosphatase, and 25-hydroxyvitamin D
  •  b. Supplemental Labs (consider adding on based on risk factors/history): Consider adding on labs for: TSH, free T4, Testosterone (in men), HbA1c or fasting glucose, 24-hr urine calcium, Serum protein electrophoresis (SPEP/UPEP), Celiac serologies (tTG IgA) if history suggests malabsorption

• 2. Diagnose: Confirm diagnosis of osteoporosis/osteopenia and attempt to correct reversible secondary causes, via history and/or imaging.

• 3. Refer/Treat: Recommend routinely prescribing vitamin D supplementation in office and correcting nutritional and lifestyle habits. Consider referral to endocrinology/rheumatology on an as needed basis. Initiate anabolic therapy when possible depending on surgical urgency (teriparatide 3-6+ months, or romosozumab if available and appropriately indicated). Of note, for cervical spine surgery, consider alternative agents to teriparatide due to the reported associations with increased implant failure.

  •  a. Urgent (<6 weeks): Optimize vitamin D and calcium; consider immediate antiresorptive if BMD is severely low
  •  b. Semi-Urgent (2-3 months): Initiate romosozumab or teriparatide immediately; delay surgery if possible to reach the 3-month mark.
  •  c. Elective (>6 months): Complete a robust 6-month anabolic lead-in for maximum screw-purchase benefit.

• 4. Plan Surgery: Consider bone augmentation (larger diameter and/or longer screws, cement augmentation, increased construct length, hydroxyapatite-coated screws, cortical bone screws) if poor bone density persists at time of surgery.

• 5. Maintenance: Recommend transitioning to anti-resorptive agents long-term to preserve any associated anabolic gains.

  •  a. Antiresorptive agents (bisphosphonates, denosumab) can usually be restarted postoperatively without negatively affecting fusion. Of note, for denosumab we recommend avoiding a delay beyond 6 months to decrease risk of rebound fractures.
  •  b. Anabolic agents (teriparatide, abaloparatide, romosozumab) may be started immediately postoperatively.
  •  c. Long-term management should include a transition to antiresorptive therapy (e.g. teriparatide approved maximum 24 months lifetime use, transition to another agent after).

Challenges and Controversies

Optimal timing and sequencing of anabolic vs anti-resorptive therapy around surgery remain common areas of debate. Anabolic therapies carry cost, barriers to access and insurance coverage, and contraindications such as cardiovascular events for romosozumab. Additionally, teriparatide’s role in the cervical spine may differ and could pose unique risks. ⁷⁵

While the clinical strategies outlined in this review are supported by the current literature, it is important to note that the underlying evidence is largely comprised of retrospective studies and observational data. The lack of high-level evidence from randomized controlled trials regarding specific preoperative intervention windows and long-term outcomes remains a limitation in the field. Consequently, the recommendations provided here should be interpreted as suggested best practices based on available data, rather than definitive clinical mandates.

Conclusion

Bone health is a critical but often underemphasized factor in spine surgery. Screening should begin in postmenopausal women, women over 65, and men over 70, while all surgical candidates benefit from risk assessment, focused laboratory testing, and bone density evaluation. In addition to DEXA, opportunistic Hounsfield Unit measurements at operative levels can provide a more direct assessment of vertebral robustness. A basic laboratory panel including: calcium, phosphate, albumin, renal function, alkaline phosphatase, and 25-hydroxyvitamin D should be performed, with additional testing dependent on history. Once low bone density is confirmed, correctable causes should be addressed and vitamin D deficiency treated, potentially initiating treatment prior to endocrinology referral. When appropriate, anabolic therapy such as teriparatide or romosozumab should be initiated for several months before surgery, paired with nutrition and lifestyle optimization. Intraoperative strategies including: longer/larger screws, cement augmentation, cortical trajectory, hydroxyapatite coating, and/or extended constructs, offer added construct strength. Postoperative and long-term management requires transition to antiresorptive therapy, since teriparatide has a lifetime maximum use of 24 months. Taking a structured approach provides surgeons with a framework to reduce fixation failure, enhance fusion, and to ultimately improve outcomes in patients with osteoporosis or osteopenia.

ORCID iDs

Mitchell K. Ng https://orcid.org/0000-0002-5831-055X

Jonathan Dalton https://orcid.org/0000-0002-7452-2712

William A. Green https://orcid.org/0000-0001-7147-0542

Alan S. Hilibrand https://orcid.org/0000-0001-8811-9687

Ethical Considerations

This in an IRB-approved study (approval #19D.508).

Consent to Participate

All patient information was de-identified and patient consent was not required. Patient data will not be shared with third parties.

Data Availability Statement

All relevant data are included in the manuscript draft, tables, and figures. The raw data are available upon reasonable request from the corresponding author.*