Osteosarcopenia in older adults undergoing transcatheter aortic valve replacement: A narrative review of mortality and frailty implications

Abstract

This narrative review examines osteosarcopenia, characterized by the concurrent loss of muscle mass and bone density, as a pivotal marker of frailty in older adults. Its implications for patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis remain underexplored. This review examines the association between osteosarcopenia and adverse clinical outcomes in older adults undergoing TAVR, with an emphasis on mortality. It also evaluates the integration of osteosarcopenia into pre-procedural risk assessments. Contemporary studies were reviewed, focusing on older adults undergoing TAVR. Key parameters included pre-procedural assessments of muscle mass (psoas cross-sectional area) and bone density (lumbar trabecular attenuation) using computed tomography. Clinical correlations with frailty indices, nutritional deficiencies, functional disability and mortality were analyzed. Studies including the FRAILTY-AVR cohort indicate that osteosarcopenia affects 15%-20% of TAVR patients and independently predicts 1-year mortality. Combined deficits in muscle and bone health are associated with elevated risks of post-TAVR complications, prolonged hospitalizations, and worsening disability compared to isolated sarcopenia or osteoporosis (P < 0.05). Incorporating osteosarcopenia into risk stratification models could enhance predictive accuracy for adverse outcomes. Osteosarcopenia serves as a critical biomarker for frailty and should be routinely assessed in pre-TAVR evaluations. Targeted interventions, such as resistance training and nutritional optimization, may mitigate its impact and improve clinical outcomes. Early identification facilitates personalized management strategies, enhancing survival and quality of life in this high-risk cohort.

Key Words: Osteosarcopenia; Frailty; Mortality; Transcatheter aortic valve replacement; Resistance training; Nutrition

Core Tip: Osteosarcopenia, the co-occurrence of muscle atrophy and bone density loss, is increasingly recognized as a potent marker of frailty in older adults undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. This review synthesizes evidence demonstrating that osteosarcopenia affects 15%-20% of TAVR patients and independently predicts 1-year mortality (P < 0.05). Compared to isolated sarcopenia or osteoporosis, osteosarcopenia correlates with higher risks of post-procedural complications, prolonged hospitalization, and functional decline. Key imaging biomarkers—psoas muscle cross-sectional area (muscle mass) and lumbar trabecular attenuation (bone density)—derived from pre-TAVR computed tomography scans provide objective frailty metrics. Integrating these parameters into risk stratification models (e.g., Society of Thoracic Surgeons Predicted Risk of Mortality) enhances predictive accuracy for adverse outcomes. Clinically, routine osteosarcopenia assessment could guide personalized interventions, such as resistance training and protein/vitamin D supplementation, to mitigate frailty-related risks. Early identification of osteosarcopenia bridges geriatric and cardiology care, offering a pathway to improve survival and quality of life in high-risk TAVR populations.

INTRODUCTION

Aortic stenosis (AS) is a leading form of valvular heart disease in older adults, with a prevalence that rises sharply with age. Among individuals over 75 years, AS affects approximately 12.4%, and severe symptomatic AS is present in 3.4% of this population[1]. Untreated severe AS carries a grave prognosis, with a two-year mortality rate exceeding 50% once symptoms develop[2]. Transcatheter aortic valve replacement (TAVR) has revolutionized the management of severe AS, providing a less invasive alternative to surgical aortic valve replacement (SAVR). TAVR has significantly reduced procedural risk and improved survival, particularly in patients with high or prohibitive surgical risk[3]. However, despite technological advancements, osteosarcopenia or frailty continue to contribute to suboptimal outcomes, underscoring the need to refine risk stratification and perioperative care strategies[4].

Osteosarcopenia represents a critical intersection of frailty, where the combined deficits in muscle and bone health exacerbate the vulnerability to stressors, such as TAVR. Osteosarcopenia, first conceptualized by Binkley et al[5] in 2009 (sarco-osteopenia), defined by the concomitant presence of low bone mineral density (BMD) and reduced skeletal muscle mass. It is increasingly recognized as a critical determinant of poor prognosis in older adults undergoing cardiovascular interventions. While frailty have been established as predictor of adverse events post-TAVR, osteosarcopenia represents an amplified risk state that predisposes patients to falls, fractures, prolonged hospital stays, and increased mortality. Recent studies show that osteosarcopenia triples 1-year mortality, doubles postoperative disability, increases heart failure, renal injury, depression and stroke risk[6-8]. This emerging syndrome reflects the interplay between musculoskeletal aging and cardiovascular pathology, providing valuable insight into the biological vulnerability of patients with severe AS. Unlike isolated sarcopenia or osteoporosis, osteosarcopenia captures a broader spectrum of frailty, making it a compelling prognostic marker in the TAVR population.

The purpose of this review is to examine the relationship between osteosarcopenia and mortality in older adults undergoing TAVR. We highlight the epidemiological significance of osteosarcopenia, delineate its pathophysiological mechanisms, and discuss its impact on clinical outcomes in patients with severe AS. By integrating insights from current literature, this review aims to advocate for the routine incorporation of osteosarcopenia assessment into TAVR preoperative protocols, fostering improved risk prediction, patient selection, and tailored rehabilitation strategies. Therefore, addressing osteosarcopenia within the context of AS represents an opportunity to enhance the quality of care and reduce procedural morbidity and mortality in this high-risk population.

PATHOPHYSIOLOGY OF OSTEOSARCOPENIA

Mechanisms

Osteosarcopenia as a biological substrate of frailty: Osteosarcopenia represents a maladaptive intersection of musculoskeletal decline and systemic frailty. Mechanistically, chronic inflammation [elevated interleukin-6 (IL-6), tumour necrosis factor alpha] and hormonal dysregulation (vitamin D deficiency, insulin resistance) drive concurrent muscle atrophy and bone resorption, exacerbating physical frailty. Clinically, osteosarcopenic patients exhibit amplified vulnerability to the 'frailty cycle': (1) Reduced mobility; (2) Increased falls; (3) Fracture risk; (4) Prolonged immobility; and (5) Further muscle/bone loss[9]. This bidirectional relationship positions osteosarcopenia as both a biomarker and accelerator of frailty in TAVR populations. Therefore, the interplay between muscle and bone deterioration in osteosarcopenia not only reflects the physical aspects of frailty but also contributes to its progression, making it a key target for intervention in frail older adults.

Molecular crosstalk in the muscle-bone axis and aortic valve stenosis: These two age-related conditions (sarcopenia and osteoporosis) share fundamental biological pathways and clinical consequences (Figure 1). Both disorders demonstrate parallel trajectories of tissue mass loss (muscle and bone respectively), driven by common mechanisms including chronic inflammation, hormonal changes, metabolic dysregulation, and comorbidites (heart failure, myocardial infarction, diabetes, etc.)[10]. The muscle-bone axis maintains systemic homeostasis through bidirectional signaling mediated by myokines and osteokines. Myocytes secrete regulatory proteins including IL-6, myostatin, irisin, insulin-like growth factor 1, and fibroblast growth factor 21, while osteocytes produce osteocalcin, sclerostin, prostaglandin E2, transforming growth factor beta, and receptor activator of nuclear factor kappa B ligand[11-13]. These molecules create a biochemical feedback loop that coordinates muscle protein synthesis with bone remodeling[14]. Adipose tissue amplifies this interplay through adipokines (leptin, resistin, adiponectin) that modulate both osteoclastic activity and skeletal muscle catabolism[15]. The endocrine effects of these factors operate through autocrine, paracrine, and systemic pathways, forming a tripartite regulatory network among muscle, bone, and fat.

Figure 1  Mechanism of osteosarcopenia and aortic valve disease.

Diagnosis of osteosarcopenia

Osteosarcopenia is diagnosed through concurrent confirmation of osteoporosis and sarcopenia using validated criteria. For osteoporosis diagnosis in postmenopausal women and men ≥ 50 years, the World Health Organization recommends central dual-energy X-ray absorptiometry (DXA) T-scores ≤ -2.5 at lumbar spine (L1-L4), femoral neck, total hip, or non-dominant distal radius. This threshold also applies to fragility fractures at hip/vertebrae (regardless of T-score) or proximal humerus/pelvis/distal forearm fractures with osteopenia (T-score -2.5 to -1.0)[16]. Sarcopenia assessment follows the Asian Working Group (AWGS) criteria requiring: (1) Low muscle mass [DXA: < 7.0 kg/m² (men)/< 5.4 kg/m² (women); bioelectrical impedance analysis (BIA): < 7.0 kg/m²/< 5.7 kg/m²]; (2) Reduced grip strength (< 28 kg/< 18 kg); and (3) Impaired function [gait speed ≤ 1 m/second, Short Physical Performance Battery (SPPB) ≤ 9, or sit-to-stand ≥ 12 seconds][17].

Additionally, five international consensus frameworks (European Working Group on Sarcopenia in Older People 2, Foundation for the National Institutes of Health, AWGS, Sarcopenia Definition and Outcome Consortium, International Working Group on Sarcopenia) guide sarcopenia evaluation, with AWGS specifically defining severe sarcopenia when all three components-low mass, weak strength, and poor function-coexist. The diagnostic integration requires meeting both systems' criteria: Osteoporosis (T-score ≤ -2.5 or fragility fracture patterns) plus sarcopenia (AWGS muscle mass thresholds with functional deficits).

PREVALENCE AND IMPACT OF OSTEOSARCOPENIA IN TAVR

Incidence rates

Osteosarcopenia, the concurrent loss of muscle mass and bone density, is a prevalent yet underrecognized condition in older adults, with particular relevance for patients undergoing TAVR. In community-dwelling older populations, prevalence rates vary widely, ranging from 5% to 37%, due to differences in diagnostic criteria and assessment methods[18]. A comprehensive meta-analysis by Huang et al[19], which pooled data from 31 studies and 15062 patients, estimated an overall prevalence of 21.0% (95%CI: 0.16–0.26). This risk was significantly higher among women [odds ratio (OR) = 5.10, 95%CI: 2.37–10.98], older age groups (OR = 1.12, 95%CI: 1.03–1.21), and those with prior fractures (OR = 2.92, 95%CI: 1.62–5.25)[19]. In TAVR candidates, such as those evaluated in large prospective cohorts, the incidence of osteosarcopenia is approximately 15%, highlighting its clinical significance in this vulnerable group[7].

Emerging data suggest significant geographic and ethnic variability in osteosarcopenia prevalence among TAVR populations. For instance, Asian cohorts report lower rates of osteosarcopenia (8%–12%) compared to European/North American populations (15%–20%), potentially reflecting differences in body composition norms, genetic predisposition, or lifestyle factors[20,21]. Notably, the FRAILTY-AVR cohort (multinational enrollment) demonstrated higher osteosarcopenia rates in White (14.9%) patients[7], though this may be confounded by regional sarcopenia diagnostic thresholds. Racial disparities are further compounded by inequities in access to TAVR—underrepresented minorities often present with advanced frailty at younger ages due to delayed referrals. Future studies must standardize osteosarcopenia criteria across diverse populations to clarify these patterns. Additionally, osteosarcopenia often coexists with frailty, further complicating accurate prevalence estimates[21]. Despite the heterogeneity in definitions, osteosarcopenia remains a pervasive condition in the TAVR population, underscoring its significance as a critical risk factor for adverse outcomes.

Epidemiological burden of osteosarcopenia

The epidemiological burden of osteosarcopenia extends beyond prevalence, as it is strongly linked to adverse outcomes. A meta-analysis of 14429 participants across prospective cohort studies demonstrated a 53% increased risk of mortality over a mean follow-up of 6.6 years (risk ratio = 1.53; 95%CI: 1.28–1.78)[22]. Among the TAVR patients, the presence of osteosarcopenia or frailty in TAVR patients is associated with an increased risk of perioperative complications, prolonged hospital stays, and higher 30-day and 1-year mortality rates (Table 1)[4,7,23-33]. This heightened risk arises from increased susceptibility to falls[30], fractures, and functional decline—key considerations for TAVR patients[31-35]. Given the variability in prevalence estimates and the profound impact on survival, there is an urgent need for standardized diagnostic criteria and routine screening in older adults, especially those with severe AS. These broad epidemiological trends provide a foundation for understanding the specific clinical implications of osteosarcopenia, as elucidated by prospective studies like the FRAILTY-AVR cohort.

Table 1 Characteristics of key studies on frailty and osteosarcopenia in transcatheter aortic valve replacement patients.

Ref.	Year	Study type	Key inclusion/exclusion criteria	Patient’s characteristics	Assessment method	Key findings
Green et al[23]	2012	Single-center prospective study	Inclusion: Age ≥ 60 years, severe calcific AS, with advanced cardiac symptoms, TAVR candidates. Exclusion: Inoperability	159 patients, mean age 86 years, 50% male	Frailty score derived from gait speed, grip strength, serum albumin, and ADL	Frailty was associated with a 35-fold increase in 1-year mortality but not with procedural complications
Green et al[24]	2015	Post hoc analysis	Inclusion: Age ≥ 60 years, severe symptomatic AS requiring TAVR, frailty assessed at 3 high-enrolling sites. Exclusion: Missing baseline frailty assessment	244 patients, mean age 86 years, 51.6% male	Frailty assessed using serum albumin, grip strength, gait speed, and Katz ADL survey	Frail individuals had higher 1-year mortality (32.7% vs 15.9% nonfrail) and poor outcomes (50% vs 31.5%)
Afilalo et al[4]	2017	Prospective multicenter cohort study	Inclusion: Age ≥ 70, severe AS, TAVR/surgical aortic valve replacement planned. Exclusion: Dementia, metastatic cancer, acute myocardial infarction < 30 days	1020 patients, mean age 82 years, 59% male	Fried, Fried+, Rockwood, and EFT etc.	EFT strongly predicted 1-year mortality (aOR = 3.72; 95%CI: 2.54-5.45), 1-year disability (aOR = 2.13; 95%CI: 1.57-2.87), and death at 30 days (aOR = 3.29; 95%CI: 1.73-6.26)
Kundi et al[25]	2019	CMS MedPAR database	Inclusion: Age ≥ 70 years, referred for TAVI (2011-2015), severe symptomatic AS. Exclusion: Declined consent	28531patients, mean age 815 years, 53.6% male	Hospital Frailty Risk Score	1-year mortality rates were 76% in low-risk patients, 17.6% in intermediate-risk patients, and 30.1% in high-risk patients (log rank P < 0.001)
Skaar et al[26]	2019	Prospective observational study	Inclusion: Age ≥ 65 years, undergoing transcatheter mitral valve repair/TAVR. Exclusion: Age < 65 years	142 patients, 54% women, mean age 83 years	A novel geriatric assessment frailty score	Geriatric assessment frailty score predicted mortality within 2 years, with an estimated HR of 1.79 (95%CI: 1.34–2.36, P < 0.001)
Goudzwaard et al[27]	2020	Prospective, observational study	Inclusion: Severe symptomatic AS patients referred for TAVI	239 patients, mean age 808 years, 49.8% male	Erasmus Frailty Score	Frailty was an independent predictor of deteriorated HR quality of life 1 year after TAVI (OR = 2.24, 95%CI: 1.07–4.70, P = 0.003)
Seoudy et al[28]	2021	Retrospective cohort study	Inclusion: Symptomatic AS, underwent transfemoral TAVR, Geriatric Nutritional Risk Index	1930 patients, mean age 82 years, 52.5% female	GNRI	After a mean follow-up of 21.1 months, all-cause mortality was significantly increased in the low-GNRI group compared with the normal-GNRI group (P < 0.001)
Arnold et al[29]	2022	PARTNER 2A trial, SAPIEN 3 intermediate-risk registry, and PARTNER 3 trial	Inclusion: Intermediate-surgical-risk or low-surgical-risk patients, Severe symptomatic AS, Enrolled in PARTNER 2A trial, SAPIEN 3 intermediate-risk registry, or PARTNER 3 trial	3025 patients, mean age 793 years, 61.6% men	Frailty was examined as a continuous variable based on grip strength, gait speed, albumin, and ADL	Increasing frailty (none vs prefrail vs frail) was associated with higher 2-year mortality (5.5% vs 11.1% vs 22.8%; log-rank P < 0.001) and worse 2-year health status among survivors (Kansas City Cardiomyopathy Questionnaire scores adjusted for baseline: 84.8 vs 79.6 vs 77.4, P < 0.001)
Strange et al[30]	2023	Danish nationwide registries study	Inclusion: Undergoing first-time TAVR, Valid Hospital Frailty Risk Score	5971 patients, median age 81 years, and 55.4% men	Hospital Frailty Risk Score	1-year risk of death was 5.8% of patients in the low frailty group compared with 10.3% of patients in the intermediate frailty group and 15.6% of patients in the high frailty group
Stein et al[31]	2024	Multicenter prospective registry	Inclusion: Pre-TAVR CT available. Exclusion: Prior valve surgery, end-stage renal disease	445 patients, median age 829 years, 41% female	3-part definition psoas muscle area indexed to height; handgrip strength; and gait speed	Among the 3 components of sarcopenia, only slower gait speed (muscle performance) was independently associated with increased post-TAVR mortality (aHR = 1.38 per 1 SD decrease (95%CI: 1.11–1.72); P = 0.004)
Persits et al[32]	2024	Retrospective cohort study	Inclusion: aged ≥ 70 years, undergoing TAVR, Pre-TAVR CT scans available. Exclusion: Emergent TAVR procedures, unstable vital signs, CT scans with fields of view excluding the abdomen	184 patients, average age 806 years, 41.8% female	Sarcopenia was defined as having both low muscle mass and either muscle weakness or poor physical performance. Frailty status was assessed using Green score	There were higher rates of the postoperative adverse events in patients with sarcopenia (54.8%) and frailty (41.9% with the Adapted Green and 50.5% with the Green-SMI score) compared to their nonsarcopenic (30.3%) and nonfrail counterparts (25.4% with the Adapted Green and 18.8% with the Green-SMI score)
Petrovic et al[33]	2024	Prospective multicentre WIN-TAVI registry	Inclusion: Women, with symptomatic severe AS, Intermediate or high surgical risk, pre-TAVR Fried frailty criteria assessment. Exclusion: Missing frailty assessment data	1019 women, mean age 82 years	Fried frailty criteria	1-year risk of the primary outcome was significantly higher in prefrail and frail (20.2%) than in nonfrail (14.9%) women (aHR = 1.51). The risk of major bleeding was higher in prefrail or frail (19.9%) than in nonfrail (10.0%) women (aHR = 2.06)
Solla-Suarez et al[7]	2024	Prospective multicenter cohort study	Inclusion: Undergoing TAVR, pre-TAVR CT scans available, Availability of HGS or gait speed measurements. Exclusion: Incomplete CT imaging, missing HGS or gait speed data	605 patients, mean age 826 years, 45% female	Osteosarcopenia was defined as a combination of low PMA and low VBD	One-year mortality was highest in osteosarcopenia (32%) followed by low PMA alone (14%), low VBD alone (11%), and normal bone and muscle status (9%) (P < 0.001)

ADL: Activity of daily living; AHR: Adjusted hazard ratio; AOR: Adjusted odds ratio; AS: Aortic stenosis; CT: Computed tomography; EFT: Essential Frailty Toolset; GNRI: Geriatric Nutritional Risk Index; HGS: Handgrip strength; HR: Hazard ratio; PMA: Psoas muscle area; TAVI: Transcatheter aortic valve implantation; TAVR: Transcatheter aortic valve replacement; SMI: Skeletal muscle mass index; VBD: Vertebral bone density.

CLINICAL EVIDENCE ON OSTEOSARCOPENIA/FRAILTY IN TAVR OUTCOMES

Key findings from the FRAILTY-AVR cohorts

The FRAILTY-AVR studies, a multicenter prospective cohort investigation, have significantly advanced our understanding of osteosarcopenia/frailty and its implications in older adults undergoing aortic valve replacement procedures, specifically TAVR and SAVR[4,7]. These studies, conducted in 2017 and 2024, provide critical insights into risk stratification and patient outcomes, with a progressive focus from general frailty to the specific syndrome of osteosarcopenia.

In 2017, Afilalo et al[4] carried out a prospective cohort study involving 1020 older adults with a median age of 82 years who were undergoing TAVR or SAVR[4]. The study revealed that frailty prevalence ranged from 26% to 68%, depending on the assessment tool employed, highlighting the necessity for a standardized approach. The Essential Frailty Toolset (EFT), a concise four-item scale evaluating lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia, emerged as the most robust predictor of adverse outcomes. The authors found that EFT-defined frailty was linked to a 3.72-fold increase in 1-year mortality [adjusted OR (aOR) = 3.72; 95%CI: 2.54–5.45], a 2.13-fold increase in worsening disability at 1 year (aOR = 2.13; 95%CI: 1.57–2.87), and a 3.29-fold increase in 30-day mortality (aOR = 3.29; 95%CI: 1.73–6.26).

Building on the 2017 findings, the 2024 FRAILTY-AVR study shifted attention to osteosarcopenia—a condition defined by the simultaneous loss of muscle mass and bone density—as a potentially more precise frailty marker in TAVR candidates. This multicenter study enrolled 605 patients aged 70 years or older with severe AS[7]. Preoperative computed tomography (CT) was used to measure psoas muscle area (PMA) and vertebral bone density (VBD), identifying osteosarcopenia in 15% of participants. The results showed that the osteosarcopenic group faced a 1-year mortality rate of 32%, compared to 9% in those with normal muscle and bone metrics (P < 0.001), while patients with isolated low PMA or low VBD showed intermediate mortality rates of 14% and 11%, respectively. Osteosarcopenia independently predicted a 3.18-fold increase in 1-year mortality (aOR = 3.18; 95%CI: 1.54–6.57) and doubled the risk of worsening disability, even after adjusting for traditional frailty measures such as the EFT and the Clinical Frailty Scale. These findings underscore the compounded prognostic impact of combined muscle and bone deterioration, suggesting that osteosarcopenia may provide greater precision in risk stratification for TAVR patients than frailty alone.

Clinically, the 2017 study introduced EFT as a practical tool for identifying at-risk patients, while the 2024 study advanced this framework by incorporating osteosarcopenia as a targeted indicator, leveraging advanced imaging to enhance outcome prediction (Table 2)[4,7]. This evolution emphasizes the value of integrating general frailty assessments with specific syndromes like osteosarcopenia into clinical practice[26], optimizing patient selection and management in both TAVR and SAVR settings.

Table 2 Evolution of osteosarcopenia/frailty assessment in aortic valve replacement of FRAILTY-AVR studies (2017 and 2024).

Characteristic	2017 study (Afilalo et al[4])	2024 study (Solla-Suarez et al[7])
Study population	1020 patients, median age 82 years (interquartile range: 77–86 years), undergoing TAVR (n = 646) or surgical aortic valve replacement (n = 374)	605 patients, aged 70 years or older (mean age 826 years ± 6.2 years), undergoing TAVR
Grouping method	Comparison of seven frailty scales: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, EFT	Assessment of osteosarcopenia using computed tomography scans to measure psoas muscle area and vertebral bone density
Follow-up period	One year for primary outcome; 30 days for secondary outcomes	One year for primary outcome; 30 days for secondary outcomes
Primary outcome	One-year all-cause mortality; 145 deaths (14%), EFT was the strongest predictor (aOR = 3.72; 95%CI: 2.54–5.45)	One-year all-cause mortality; 84 deaths (13.9%), osteosarcopenia associated with a 318-fold increase (aOR = 3.18; 95%CI: 1.54–6.57)
Secondary outcomes	30-day mortality: 4.2% (43 deaths), EFT aOR = 3.29 (95%CI: 1.73–6.26). Composite of death or worsening disability at one year: 35% incidence (357/1,020), EFT aOR = 2.13 (95%CI: 1.57–2.87)	30-day mortality: 3.6% (21 deaths), hospital length of stay: Mean 6.5 days ± 8.0 days, discharge not to home: 20.5% (120/585), worsening disability at one year: 40.6% (215/529), osteosarcopenia OR = 2.11 (95%CI: 1.19–3.74)

AOR: Adjusted odds ratio; EFT: Essential Frailty Toolset; TAVR: Transcatheter aortic valve replacement.

Osteosarcopenia versus isolated sarcopenia: Distinct prognostic implications

Although isolated sarcopenia is a known risk factor for poor outcomes following TAVR, its impact is significantly amplified when combined with osteoporosis as osteosarcopenia. The FRAILTY-AVR cohort demonstrates that osteosarcopenia triples the mortality risk compared to isolated deficits. This synergistic effect likely reflects the combined contributions of muscle and bone loss, which exacerbate frailty, heighten fall and fracture risk, and hinder postoperative recovery[36]. In contrast, patients with isolated sarcopenia may retain sufficient bone integrity to partially offset functional decline, whereas osteosarcopenia signals a more severe state of musculoskeletal compromise, reducing resilience to surgical stress[37]. These observations highlight the need for comprehensive assessments that integrate both sarcopenic and osteoporotic parameters into preoperative evaluations, allowing for the identification of high-risk subgroups who may benefit from tailored interventions such as prehabilitation, nutritional support, and post-TAVR rehabilitation programs.

SCREENING AND DIAGNOSIS

Preoperative assessments

Accurate identification of sarcopenia and osteosarcopenia prior to TAVR is essential for risk stratification and optimizing clinical outcomes. Routine preoperative imaging, specifically CT, offers a valuable opportunity to assess musculoskeletal health without the need for additional tests[38]. Cross-sectional imaging of the PMA at the L3-L4 vertebral level is widely used to evaluate muscle mass, while VBD is assessed through Hounsfield unit (HU) measurements of trabecular bone on the same CT scan[39]. These opportunistic assessments allow for the simultaneous evaluation of sarcopenia and osteoporosis, facilitating the diagnosis of osteosarcopenia.

Thresholds for diagnosing sarcopenia typically include PMA values of < 22 cm² in men and < 12 cm² in women, while low VBD is often defined by measurements below 90 HU[40]. Notably, osteosarcopenia—characterized by concurrent low PMA and VBD—has demonstrated superior predictive value for postoperative mortality and disability compared to isolated measures of sarcopenia or osteoporosis[40]. Incorporating these assessments into routine TAVR workups enhances risk prediction models, such as the TAVI2-SCORE, by providing a more comprehensive evaluation of frailty. In addition to CT, DXA and BIA remain viable alternatives for assessing muscle mass and bone density. However, these modalities are less frequently utilized in the TAVR setting due to limited availability and logistical constraints. Emerging automated algorithms for CT-based sarcopenia and osteosarcopenia assessment are anticipated to streamline preoperative screening, further integrating musculoskeletal evaluation into standard cardiovascular workflows.

Cost-effectiveness of CT-based osteosarcopenia screening

While CT provides precise musculoskeletal phenotyping, its routine use for osteosarcopenia screening raises cost-effectiveness concerns. In the United States, a dedicated abdominopelvic CT costs approximately 500$–1200$, whereas opportunistic measurements during pre-TAVR CT angiography add minimal expense. A Markov model analysis estimated that CT-based osteosarcopenia screening could be cost-effective if it reduces 1-year mortality by ≥ 5% (current data: 12% absolute reduction), though this assumes universal access to post-TAVR rehabilitation—a limitation in resource-constrained settings[41]. For clinics without advanced imaging, pragmatic alternatives like strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire + FRAIL scale may suffice, albeit with lower sensitivity. Future value-based analyses should weigh CT’s prognostic benefits against implementation barriers in low-income regions.

Functional assessments

While imaging provides a structural assessment of muscle and bone health, functional evaluations are critical for quantifying the clinical impact of sarcopenia. The SPPB is one of the most widely used tools for assessing lower extremity function and frailty[42]. It comprises gait speed, balance, and chair rise tests, with scores ≤ 8 indicating poor physical performance and heightened procedural risk. Low gait speed (< 0.8 m/second) has been independently associated with increased mortality and morbidity following TAVR[43].

Handgrip strength, measured using a dynamometer, serves as an additional indicator of sarcopenia, with thresholds of < 27 kg for men and < 16 kg for women representing diminished muscle strength[44]. This simple, cost-effective test correlates strongly with overall frailty and predicts adverse outcomes in the perioperative period. The SARC-F questionnaire, a self-reported screening tool assessing strength, ambulation, rising from a chair, stair climbing, and falls, offers a practical method for identifying patients at risk for sarcopenia[45]. Although less precise than direct muscle measurements, SARC-F facilitates large-scale screening and prioritizes patients for further evaluation.

Combining imaging with functional assessments provides a multidimensional perspective on frailty, enhancing the ability to identify high-risk patients and personalize perioperative management strategies. Integrating these evaluations into routine TAVR protocols holds promise for improving long-term outcomes and reducing procedural complications.

MANAGEMENT STRATEGIES

High-intensity resistance training

Multiple studies from the Franconian Osteopenia and Sarcopenia Trial demonstrate that high-intensity resistance training (HIRT), often combined with whey protein, vitamin D, and calcium supplementation, significantly improves skeletal muscle mass index (SMI), BMD, and functional strength in older men with osteosarcopenia. For instance, a 12-month HIRT intervention maintained lumbar spine BMD and increased SMI, with significant between-group differences compared to controls [standardized mean difference (SMD) = 0.90 and SMD = 1.95, respectively][46]. Extending HIRT to 18 months further enhanced lumbar spine and total hip BMD (SMD = 0.72 for both) and sarcopenia Z-scores (SMD = 1.40)[47]. These benefits were supported by high adherence (95%) and no reported injuries, underscoring HIRT’s feasibility and safety[48]. Detraining effects highlight the need for continuous intervention. After 6 months of detraining following 18 months of HIRT, significant losses in SMI, leg strength, lean body mass, and cardiometabolic health (metabolic syndrome Z-score) were observed, though some overall benefits persisted (P ≤ 0.004)[48]. This suggests that intermitted training with prolonged breaks may undermine long-term efficacy.

Nutritional supplementation

Nutritional augmentation, particularly with whey protein (1.5–1.6 g/kg/day), amplified HIRT’s effects on muscle mass and strength. After 28 weeks, HIRT plus protein significantly improved sarcopenia Z-scores (P < 0.001), SMI, and handgrip strength compared to controls[49]. However, HIRT’s impact on fat infiltration varied by muscle group. While thigh muscle intermuscular adipose tissue volume stabilized after 16 months of HIRT (P = 0.004 vs increase in controls)[50], no significant reduction in paraspinal muscle fat infiltration was observed after 16 months, despite BMD gains. Similarly, visceral adipose tissue (VAT) decreased significantly (-7.7%, P < 0.001) after 18 months of HIRT, but abdominal aortic calcification progressed independently of exercise.

Alternative interventions

Beyond HIRT, leucine-enriched whey protein supplementation (1.5 g/kg/day) alone or with resistance exercise improved cardiometabolic markers in older adults after 16 weeks, reducing low-density lipoprotein cholesterol, insulin, and Homeostasis Model Assessment of Insulin Resistance (P < 0.05)[51]. Vitamin D supplementation (50000 IU bolus plus 1000 IU/day) increased circulating osteoprogenitor cells by 52% (P < 0.001) over 6 weeks, indicating a potential role in mesenchymal precursor regulation[52,53]. However, zoledronic acid, a bisphosphonate, improved BMD at the hip and spine over 2 years but did not enhance appendicular lean mass in older women.

Pharmacological approaches

Pharmacological interventions targeting sarcopenia and osteosarcopenia remain an area of ongoing investigation. Currently, no Food and Drug Administration-approved medications specifically address sarcopenia; however, several agents have shown promise in clinical trials. Selective androgen receptor modulators (SARMs) have demonstrated potential in increasing lean muscle mass and enhancing physical function, although their long-term safety profile warrants further evaluation. Myostatin inhibitors, which prevent muscle degradation by blocking the myostatin pathway, represent another novel therapeutic avenue[54]. Testosterone replacement therapy has been explored in men with low endogenous levels, yielding modest improvements in muscle mass and strength[55]. However, its use is limited by potential cardiovascular risks and the need for careful monitoring. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have also been investigated for their role in mitigating muscle wasting, with evidence suggesting that they may enhance mitochondrial function and reduce inflammation[56]. Bisphosphonates and denosumab, commonly used in the treatment of osteoporosis, are critical in managing the bone component of osteosarcopenia. Additionally, depression and cognitive dysfunction are common in patients that undergo TAVR and are associated with increased mortality and worse quality of life. Statin, which are commonly used among TAVR patients, could safely and effectively improve the symptoms of depression and inflammation status among depressive patients[57]. These agents reduce fracture risk and preserve BMD, complementing exercise and nutritional interventions aimed at preventing falls and disability.

Therefore, HIRT consistently emerges as an effective, safe intervention for improving BMD, muscle mass, and strength in osteosarcopenic men, with nutritional support enhancing outcomes. However, its limited effect on muscle fat infiltration and VAT suggests that additional strategies (e.g., aerobic exercise) may be needed to address metabolic components comprehensively. Detraining data underscore the importance of sustained exercise, as even short breaks erode gains, particularly in muscle quality and cardiometabolic health.

FUTURE DIRECTIONS

Need for standardized diagnostic criteria

A major limitation in the management of sarcopenia and osteosarcopenia in TAVR patients is the absence of standardized diagnostic criteria. Current definitions and cutoffs for sarcopenia and low bone density vary across studies, leading to inconsistencies in prevalence estimates and prognostic assessments[58]. Harmonizing diagnostic thresholds for PMA and VBD using CT or DXA is essential to ensure uniform identification of high-risk patients[59]. International collaboration aimed at developing consensus guidelines will enable more accurate stratification and targeted interventions, ultimately improving clinical outcomes.

Clinical trials and research

Ongoing and future clinical trials are critical for advancing the management of osteosarcopenia in TAVR patients. Trials such as the PERFORM-TAVR (NCT03522454) are investigating the efficacy of prehabilitation programs incorporating exercise and nutritional supplementation. Additionally, randomized controlled studies assessing pharmacologic agents, including myostatin inhibitors and SARMs[60] and stem cell therapy[61], are expected to yield insights into novel therapeutic pathways. Additionally, new biomaterials of aortic valve[62] and improvement of micro-circulation dysfunction by cardiac shock wave therapy[63] could decrease the rate of rehospitalization among patients with heart failure.

The optimal intervention strategy for AS patients with comorbidites (coronary artery disease, hypertrophic cardiomyopathy) is a research hot topic. The optimal timing for percutaneous coronary intervention (PCI) in patients undergoing TAVR is debatable[64,65]. Searching the Society of Thoracic Surgeons/American College of Cardiology transcatheter valve therapy Registry and Medicare Linkage, a recently published study showed patients undergoing concomitant PCI and TAVR had higher major vascular complications, and higher risk of all-cause mortality and stroke compared with those who underwent PCI within 90 days before the TAVR procedure[66]. However, meta-analysis demonstrated that among patients undergoing TAVR who required PCI, no significant differences were observed in the early and long-term outcomes between those receiving concurrent TAVR and PCI versus staged surgery[67]. Furthermore, the co-existence of AS and obstructive hypertrophic cardiomyopathy is not uncommon, and treatment with aficamten could result in a significantly greater improvement in quality of life[68]. Surgical intervention is the gold standard management, and it is important to measure the quality of life and functional improvement among patients with severe AS and HCM undergoing TAVR[69]. However, TAVR outcomes are unclear in this population. Continued research focusing on integrating imaging biomarkers and functional assessments will refine perioperative risk models, fostering precision medicine approaches in the management of frail older adults undergoing TAVR.

CONCLUSION

Osteosarcopenia represents a critical, yet underrecognized, predictor of adverse outcomes in older adults undergoing TAVR. Its dual impact on muscle and bone health amplifies frailty, increasing the risk of mortality and disability. Integrating standardized diagnostic criteria, prehabilitation strategies, and nutritional support into routine care can improve quality of life and heart function, and improve postoperative recovery after cardiac surgery[70]. Future research and clinical trials will integration in biomedical science[71], further refine therapeutic approaches, enhancing patient selection and outcomes. Addressing osteosarcopenia holistically within cardiovascular care is essential to optimizing long-term success in this vulnerable population. By operationalizing osteosarcopenia as a measurable frailty phenotype, clinicians can better risk-stratify TAVR candidates and tailor interventions to break the cycle of musculoskeletal decline.