1Osteopathic Medicine, Philadelphia College of Osteopathic Medicine, Suwanee, GA, United States
2Osteopathic Medicine, Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States
3Mayo Clinic, Phoenix, AZ, United States
Correspondence: Mustafa Ansari Osteopathic Medicine, Philadelphia College of Osteopathic Medicine, 625 Old Peachtree Rd NW, Suwanee, GA 30024, United States. Tel: +1-678-225-7500 Fax: +1-678-225-7526 E-mail: ma3458@pcom.edu
• Received: September 20, 2025 • Revised: April 13, 2026 • Accepted: May 11, 2026
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Musculoskeletal injury risk in midlife women has traditionally been attributed to estrogen decline, but this narrow focus overlooks the broader biomechanical, neuromuscular, and structural changes associated with menopause. Estrogen plays a multisystem role in maintaining trabecular bone integrity, collagen turnover, and neuromuscular coordination. Its abrupt loss causes bone demineralization (2%–5% annually in early menopause), impairs tendon repair, and contributes to sarcopenia. Fluctuating estradiol levels during perimenopause may transiently increase ligament laxity, further destabilizing joints. Common injuries such as Achilles and rotator cuff tendinopathies, plantar fasciitis, and stress fractures are amplified by low bone mineral density, prior fracture history, aromatase inhibitor use, and rapid increases in physical activity. Although early initiation of hormone replacement therapy reduces fracture risk by 20%–40%, it is not appropriate for all patients due to contraindications and individualized risk–benefit profiles. Non-hormonal strategies—including resistance training, nutritional optimization, and early screening with dual-energy X-ray absorptiometry and peripheral quantitative computed tomography—remain underutilized, particularly among marginalized populations. This structured narrative review synthesizes evidence from endocrinology, biomechanics, and musculoskeletal epidemiology to evaluate limitations in current research, including reliance on observational data, homogeneous cohorts, and technocentric approaches with limited generalizability. Future efforts should prioritize personalized, hormone-informed exercise prescriptions, biomarker-guided monitoring, and community-based prevention strategies. The prevailing estrogen-centric paradigm may benefit from a broader multidisciplinary framework integrating biological, mechanical, and social determinants of injury risk. We propose a hormone–tissue–load mismatch model that reframes menopause as a modifiable biomechanical window for injury prevention.
Overuse injuries and stress fractures are prevalent musculoskeletal conditions, often resulting from repetitive mechanical loading that exceeds tissue repair capacity [1]. Among midlife women, the incidence of these injuries is influenced by the physiological changes associated with menopause and perimenopause, periods marked by profound hormonal and structural alterations. The perimenopause phase is reported to last for an average of 4–7 years, though it can last up to 14 years, and the average age of menopause is 51–52 years in the US [2]. Perimenopause, which can last 4 years, is characterized by fluctuating estrogen and progesterone levels, followed by an abrupt decline post-menopause. These hormonal shifts significantly impact bone integrity, muscle mass, and connective tissue properties, predisposing women to biomechanical vulnerabilities [3]. Unlike prior reviews that focus primarily on bone mineral density (BMD) or fracture outcomes, this review critically examines how endocrine-driven tissue vulnerability interacts with mechanical loading to precipitate overuse injuries before overt osteoporosis develops.
Estrogen is critical in maintaining bone homeostasis by modulating osteoclast and osteoblast activity. Postmenopausal estrogen deficiency accelerates bone resorption resulting in an average annual BMD loss of 2%–3% annually during early menopause, with cumulative losses approximating 10% over the first five years. Studies report that nearly 20% of total lifetime bone loss occurs in this early postmenopausal period [4]. Trabecular bone, found in high-stress regions such as the tibia and pelvis, is particularly affected, resulting in compromised load-bearing capacity and increased susceptibility to stress fractures. These biomechanical changes coincide with lifestyle factors such as increased physical activity among midlife women seeking cardiovascular and weight control benefits, which, paradoxically, can elevate injury risk if not appropriately managed. Epidemiological data indicate that the prevalence of stress fractures in postmenopausal women engaged in recreational or endurance activities is nearly double that observed in premenopausal counterparts [5]. Given the growing participation of women over 40 in recreational sports and structured exercise programs, understanding the interplay between hormonal decline and musculoskeletal vulnerability is clinically significant [6].
Tendon elasticity and collagen synthesis are also diminished under hypoestrogenic conditions, leading to an increased risk of tendinopathies and other overuse syndromes. In midlife and older women, such overuse injuries and stress fractures not only affect physical function but also contribute to long-term morbidity, including chronic pain and reduced quality of life [7]. This review critically examines the current evidence linking menopausal and perimenopausal hormonal shifts to structural strain, overuse injuries, and stress fractures with emphasis on underlying mechanisms, risk factors, and preventive strategies.
METHODS
This review was conducted as a structured narrative review to analyze current evidence and identify mechanistic and clinical gaps. Electronic searches were performed in PubMed, Scopus, and Web of Science using combinations of the terms: menopause, perimenopause, estrogen, stress fracture, overuse injury, tendinopathy, bone microarchitecture, and sarcopenia. Inclusion criteria comprised English-language human studies published between 2010 and 2025, with priority given to randomized controlled trials (RCTs), longitudinal cohort studies, biomechanical analyses, and high-resolution imaging studies. Exclusion criteria included case reports, non-peer-reviewed sources, and studies without sex-specific data. Evidence quality was appraised qualitatively based on study design, population relevance, and methodological transparency.
We introduce the hormone–tissue–load mismatch model, which posits that menopausal injury risk emerges not solely from estrogen deficiency, but from a temporal mismatch between declining tissue resilience (bone, tendon, muscle) and maintained or increased mechanical loading. During perimenopause, fluctuating estradiol (E2) alters ligament compliance and neuromuscular control, while early postmenopause accelerates microarchitectural bone loss and sarcopenia. When physical activity intensifies without adaptive recovery capacity, repetitive sub-threshold loads accumulate, culminating in overuse injury or stress fracture.
Hormonal changes in menopause and perimenopause
Menopause results in a significant decline in circulating levels of estrogen and progesterone. In addition to changes in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, there is a substantial decrease in the amount of estrogen produced during menopause [8]. Estrone (E1), derived from peripheral aromatization of androstenedione, becomes the predominant, but significantly less potent, estrogen [9]. Estriol (E3) remains negligible outside of pregnancy. Progesterone, dependent on corpus luteum activity, ceases following ovulatory failure, leading to neuroendocrine and musculoskeletal changes. E1 without the presence of progesterone may cause endometrial hyperplasia with/despite an overall low estrogen tone [10].
Menopause derived estrogen deficiency has pronounced systemic consequences. However, it’s most clinically relevant consequences for this review relate to the musculoskeletal system. Reduced estrogen signaling alters bone remodeling through increasing osteoclast activity and reducing osteoblast function. This leads to accelerated bone loss and impaired microdamage repair. In parallel, declines in collagen synthesis and tendon elasticity reduces the mechanical resilience of connective tissues. Sarcopenia and impaired neuromuscular control diminish load absorption [11]. Collectively, these changes reduce the capacity of bone, tendon, and muscle to tolerate repetitive loading, increasing susceptibility to overuse injuries and stress fractures during the menopausal transition [12].
Estrogen also plays a vital role in bone metabolism. Estrogen receptor alpha (ERα), which dominates in cortical bone, regulates osteoblast and osteoclast activity. Estrogen receptor beta (Erβ) in trabecular bone has modulatory effects, and G-protein coupled estrogen receptor 1 (GPER1) ensures the survival of osteocytes via non-genomic signaling [13]. With estrogen loss, osteoclastogenesis increases due to high receptor activator of nuclear factor kB ligand (RANKL) and low osteoprotegerin, while osteoblastogenesis drops due to impaired Wnt/β-catenin signaling and raised tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels [14]. Trabecular bone score (TBS) loss of around 6.3% within the first five years post menopause [15]. Overall, these receptor-level changes will manifest as accelerated osteoporosis, increasing the fragility of the joints.
Beyond bone, estrogen deficiency degrades ligaments and tendons due to loss of ERβ signaling, elevated matrix metalloproteinases-1 and -3 (MMP-1/3), and reduced elastin, destabilizing joints [16]. Muscles suffer from reduced satellite cell activation, advancing sarcopenia. Neuromuscular junctions lose acetylcholine receptor stability, slowing contraction and proprioception [17]. These molecular changes present clinically with slower tendon healing, joint instability, and increased overuse injury. Apart from the molecular level, Perimenopause also features hormonal fluctuations rather than a steady decline. E2 may spike to 300 pg/mL, while FSH stays >25 IU/L due to inhibin B loss. These surges can temporarily increase ligament laxity, heightening joint instability risk. Postmenopause, E2 stabilizes below 20 pg/mL, leading to progressive degradation of muscle and connective tissue, increasing risks for tendinopathy, rotator cuff tears, and stress fractures [18].
The hormonal shifts of menopause represent a systemic endocrine failure with biomechanical consequences. Disruption of ER signaling, inflammation, and tissue architecture explains the elevated risk of fractures and injuries [19]. Hormone therapy is time-sensitive, with early initiation preserving bone health, whereas late use offers minimal benefit. Future therapeutic strategies should prioritize targeting selective ER modulation for musculoskeletal protection while minimizing cancer risk as it has agonist and antagonist activities [20].
To synthesize these endocrine and metabolic mechanisms into clinically relevant musculoskeletal outcomes, Table 1 summarizes key hormonal and physiologic changes observed during menopause and perimenopause, their effects on bone, tendon, and muscle tissue, and corresponding preventive strategies relevant to rehabilitation and injury prevention.
Structural and biomechanical consequences of menopause and perimenopause in relation to overuse injuries and stress fractures
Estrogen decline boosts bone resorption, outpacing formation. Within the first 3–10 years post-menopause, trabecular bone loses 2%–3% annually, while cortical bone declines by about 1% annually. Sites rich in trabecular bone, such as the vertebrae, hips, and distal tibia, are most vulnerable. Concurrently, cortical thinning and porosity reduce stiffness and load capacity, raising fracture risk [21]. Low estrogen levels also impair bone repair by preventing adequate remodeling of microcracks, a natural result of loading, by reducing remodeling activation. This leads to incomplete resorption and delayed mineralization. Unrepaired microdamage weakens trabecular structure and cortical strength, increasing fracture risk. In addition, osteocytes become less responsive to strain, further limiting adaptive remodeling [22]. As a result of all these changes, stress fractures are more likely to occur under loads that would otherwise be well tolerated.
Estrogen deficiency also weakens tendons and ligaments by decreasing collagen synthesis, fibril regulation, and hydration. These changes reduce tensile strength and elasticity. Furthermore, increased advanced glycation end products (AGEs) stiffen collagen, impairing load distribution and increasing tendinopathy risk. Diminished lower tissue elasticity also increases injury risk by raising skeletal strain [23].
Menopausal-induced sarcopenia can also lead to losses in muscle strength, altered gait mechanics, and amplified bone fragility. Reduced type II fibers and neuromuscular control impairs shock absorption and leads to gait changes, which include shorter strides, wider steps, and greater hip abductor use. Kyphosis from vertebral fractures shifts the center of gravity forward, overloading the lower limbs. Ground reaction force redistribution adds stress to already weakened bones, promoting stress fractures [24]. Together, compromised bone, tissue repair, and neuromuscular changes create a structurally vulnerable system. Preventive strategies must focus on bone, muscle, and biomechanical support during menopause [25].
Overuse injuries in menopausal and perimenopausal women
Overuse injuries rise during menopause due to hormonal decline, structural weakening, and biomechanical changes. Tendinopathies, especially Achilles and rotator cuff injuries, are the most common. Achilles tendons face repetitive eccentric load plus poor collagen synthesis, leading to stiffness and microtears. Rotator cuff tendons with high functional demand suffer matrix and vascular changes leading to chronic tendinopathy and partial tears [26]. Plantar fasciitis, linked to foot muscle weakening, arch collapse, and altered gait, is frequent. Poor shock absorption and tendon compliance cause microdamage to the plantar fascia, leading to chronic inflammation and degeneration [27].
Sarcopenia caused by estrogen loss reduces type II fibers, weakening joint stabilization and shock absorption. Concurrently, estrogen withdrawal disrupts tenocyte metabolism and extracellular matrix (ECM) turnover, leading to reduced collagen and hydration, increasing AGEs and tendon stiffness. Mechanical loading further activates ECM, interleukin-1 beta (IL-1β), and matrix metalloproteinase-9 (MMP-9), which break down collagen and induce tendon apoptosis. Together, these changes slow down the healing process and promote degeneration [28]. Years of cumulative loading work and exercise, combined with poor vascularity, low cell proliferation, and impaired matrix deposition, means that repetitive stress now exceeds repair capacity and can progresses to chronic injuries. Clinically, this explains why menopausal women tend to have more tendinopathies that are either chronic, recurrent, and/or resistant. The interaction of hormonal, neuromuscular, and molecular changes significantly raises the risk of Achilles tendinopathy, rotator cuff tears, and plantar fasciitis. These reduce mobility and increase fracture risk and disability. Effective prevention, therefore, requires a focus on muscle preservation, tendon resilience, and hormone support during and after menopause [29].
Stress fracture epidemiology in midlife and older women
Stress fractures are significantly more prevalent in midlife and older women compared to premenopausal counterparts, largely due to estrogen decline and age-related structural changes. Large-scale analyses demonstrate that women over 50 experience markedly higher rates of lower-extremity stress fractures involving the tibia, metatarsals, and proximal femur than men or younger women [30]. In perimenopausal cohorts, fracture incidence (including low-energy fractures) ranges from 5.6% to 8.5% over 2–3.6 years with common sites being the wrist (37%), ankle (12%), hands, feet, ribs, and hip [31]. Women sustaining perimenopausal fractures exhibit a 5.8% lower lumbar spine BMD and 4.6 lower femoral BMD compared to non-fracture controls [32].
Postmenopausal women with metatarsal stress fractures have significantly lower dual-energy X-ray absorptiometry (DXA) scores compared with premenopausal women despite similar body mass index (BMI) and vitamin D status, confirming a direct link between menopausal status and skeletal fragility [33]. Key risk factors include low BMD (each 1-standard deviation decrease in spinal or femoral BMD raises risk by 1.4–1.6-fold), absence of hormone therapy (relative risk [RR] 1.5–2.2 for osteoporotic fractures), prior fractures (hazard ratio [HR] 1.25–1.33), chronic illness (RR 1.4–1.6), smoking (RR 1.8), and high alcohol intake (odds ratio [OR] ~1.45) [31,34,35]. Mechanistically, estrogen withdrawal accelerates trabecular bone and compromises microdamage repair, lowering fracture thresholds under repetitive loads, even before osteoporosis becomes overt [36]. These combined effects highlight the importance of targeted preventive measures during the menopausal transition.
Bone quality vs. quantity
Although areal BMD quantifies mineral content, menopause induces severe bone quality deterioration that functionally undermines skeletal integrity. Estrogen loss triggers rapid cortical porosity through intracortical remodeling. Studies of populations in Australia showed an annual porosity increases of about 0.44% in premenopause, 0.80% during perimenopause, and 1.40% postmenopause; this cortical change accounted for nearly 80% of appendicular bone loss despite modest trabecular declines (~0.17%–0.31% bone volume fraction [bone volume/total volume] per year) [37]. High-resolution peripheral quantitative computed tomography (pQCT) studies confirm cortical porosity is a dominant determinant of bone strength in postmenopausal women (semi‑partial R2≈0.22 at the tibia) and predicts nonvertebral fracture risk, independent of BMD and Fracture Risk Assessment Tool (FRAX) scores [38]. Cortical thinning and area loss further compound fragility, especially when advanced tools show porosity contributions beyond what FRAX or Garvan captures [39].
Concurrently, trabecular architecture deteriorates after age 50, characterized primarily by the loss of connectivity and trabecular number rather than simple thinning. This leads to the production of discontinuous rod-like structures with fewer load-bearing elements [40]. In vivo comparisons demonstrate postmenopausal women experiencing 3%–8% declines in cortical tissue mineral density alongside increased porosity, regardless of ethnicity [41]. These fine structural deficits–such as cortical porosity, sparse trabecular nodes, and reduced tissue density–compromise both mechanical strength and microdamage repair. This sharply reduces failure thresholds under repetitive stress, even when BMD remains above osteoporotic thresholds. Advanced microarchitecture measures thus add critical prognostic value beyond BMD alone [42]. Put simply, even women with normal BMD scores have higher fracture risks if the microarchitecture is compromised, demonstrating the need for more imaging or biomarkers.
Interaction with physical activity
Midlife women frequently increase exercise, like weight-bearing or high-impact activities, for weight control and metabolic benefit. Although resistance and impact training can stimulate osteoblast activity, preserve bone mass, and lower osteoporosis risk (in postmenopausal women, regular exercise reduced incident osteoporosis by ~17%; HR 0.83; 95% confidence interval [CI] 0.71–0.97) [43]. Abrupt intensification of loading during accelerated bone loss can overwhelm diminished microdamage repair capacity. Stress fractures often arise in postmenopausal women who initiate vigorous regimens without gradual progression when coupled with low BMD, protein or calcium inadequacy, or sarcopenia [44].
Estrogen deficiency impairs targeted bone remodeling while amplifying cortical porosity and trabecular weakening. As a result, even moderate repetitive stresses—such as increased running mileage—can exceed the fatigue thresholds of weakened bone. A survey in female runners (mean age ~35–54) identified that osteopenia (OR 4.14), previous tendon injuries (OR 1.49), running >20 miles/week (OR 1.74–1.77), and amenorrhea/bracketing menstrual disturbances (RR≥2) raised stress‑fracture risk significantly [45]. Sarcopenia further limits dynamic load absorption, shifting stress to compromised bone. Thus, while physical activity remains essential, an optimal strategy during menopause is centered around progressive loading, strength training, nutritional support, and careful monitoring to avoid exceeding the bone’s reduced fatigue resistance threshold.
Additional risk factors
Additional risk factors that compound stress fracture risk in midlife women include nutritional deficits and medication exposures that exacerbate bone fragility. Inadequate calcium intake (below the recommended 1,000–1,200 mg/day) and vitamin D deficiency–common in older women due to reduced dietary absorption, limited sun exposure, obesity, or drug interactions–trigger secondary hyperparathyroidism. The resulting metabolic cascade elevates bone turnover, impairs mineralization, and weakens proximal muscles, which increases fall and fracture risk [46]. Although calcium and vitamin D supplementation improves serum levels, large-scale analyses suggest minimal fracture reduction benefit, prompting critical re-evaluation of universal supplementation policies.
Estrogen‐depleting medications such as aromatase inhibitors (AIs) (e.g., anastrozole, letrozole, exemestane) dramatically increase fracture risk beyond what is expected from menopause alone. Meta‐analyses encompassing nearly 100,000 women show pooled RR of osteoporotic fractures ~1.35 (95% CI 1.29–1.42) and vertebral fractures RR ~1.83 during AI therapy compared to tamoxifen or no AI use [47]. Observational data report fracture risks in AI-treated women up to 40% higher (HR ~1.40) than tamoxifen users, though elevated baseline BMI and BMD may mitigate observed fracture incidence in some cohorts [48].
AI therapy accelerates bone loss by an additional 2%–3% annually in trabecular-rich regions and increases cortical porosity through unchecked remodeling in estrogen-deprived bone [49]. Combined, nutritional insufficiency and AI‐induced estrogen deprivation imposes a dual insult: diminished bone mass, degraded microarchitecture, compromised mineralization, and slowed microdamage repair. This synergistic effect sharply lowers skeletal fatigue resistance, contributing to a higher incidence of stress fractures and fragility fractures in menopausal and perimenopausal women. Since AI therapy has been seen to increase risks of fracture through various pathways, women on these medications should be screened earlier and more aggressively for earlier intervention.
Role of estrogen and hormone therapy in injury prevention
Hormone replacement therapy (HRT), consisting of estrogen with or without progestogen, has been demonstrated in multiple RCTs and meta-analyses to significantly reduce fracture risk and increase BMD in postmenopausal women. A meta-analysis of 28 trials (33,426 women) found HRT reduced total fracture risk by 26% (RR ~0.74; 95% CI 0.69–0.80), hip fracture by ~28%, and vertebral fracture by ~37% compared to placebo or no therapy [50]. In the Women’s Health Initiative (WHI) trial, combined conjugated equine estrogen and medroxyprogesterone acetate decreased risk of any fracture by ~24% (HR 0.76; 95% CI 0.69–0.83), hip fractures by ~30% (HR 0.66; 95% CI 0.45–0.98) and wrist/vertebral fractures with similar reductions, while raising total hip BMD by ~3.7% over three years versus 0.14% in the placebo group [51]. Benefits appear strongest when HRT is initiated before age 60 or within 10 years of menopause onset; fracture protection diminishes when started later than 60, and the anti-fracture effect wanes after cessation [51].
Prospective cohort data (OSTPRE, Finnish study; n≈7,217 women age 47–56) similarly report ~31%–38% reduction in any fracture and distal forearm fractures with HRT use (adjusted HR ~0.67 and 0.53, respectively) over five years [52]. Systematic reviews indicate vertebral fracture reductions of approximately 33% especially in women younger than 60 or with osteoporosis and non-vertebral fractures by ~27% (RR 0.73; 95% CI 0.56–0.94), though efficacy declines in older age groups (≥60) [53]. In frail elderly women (≥75 years), HRT increased lumbar spine BMD by ~4.3% and total hip by ~1.8% over nine months with substantial reductions in bone-turnover markers [54]. Overall, estrogen‐based HRT clearly enhances bone quantity (BMD) and microarchitectural stability, translating into 20%–40% reductions in vertebral, hip, and overall fractures when started early in menopause. However, declining benefit with delayed initiation, and risk considerations (e.g., thromboembolism, cardiovascular and breast cancer risk), require individualized risk-benefit assessment before prescribing HRT [55].
Non-hormonal interventions
Exercise programs combining impact (e.g., jumping, step aerobics) and resistance training (e.g., weight‑lifting, vest‑jump work) produce modest but clinically meaningful gains in BMD for postmenopausal women: meta-analysis showed that moderate intensity resistance training was superior in improving lumbar spine bone mineral density (LS BMD) and femoral neck bone mineral density (FN BMD) compared to the control group (as per usual daily life), with a statistically significant difference (p<0.05) [56]. One RCT in breast cancer survivors found resistance+impact training preserved spinal BMD (‑0.47% vs. ‑2.13% in controls) and attenuated elevated bone turnover markers (osteocalcin, deoxypyridinoline). Meta-analyses indicate that combined and multicomponent exercise yields the most consistent benefit at both the spine and hip, though the quality of evidence is rated low to moderate [57].
Nutritional strategies also play a key adjunct role. Adequate daily intake of calcium (1,000–1,200 mg), vitamin D (600–800 IU), protein (1.0 g/kg/day), magnesium, vitamin K2, and antioxidants like vitamin E correlate with better BMD maintenance and lower fracture risk in postmenopausal populations [58]. Vitamin K2 supports osteocalcin carboxylation and bone mineralization, while phytoestrogens and phytates may modestly inhibit osteoclastic resorption and contribute to bone preservation [59].
Collectively, evidence supports strategically dosed, multi-modal exercise programmes–incorporating weight-bearing and resistance training several times a week–along with nutrition strategies emphasizing adequate protein and diverse micronutrients. These non-hormonal approaches help to maintain bone density, improve muscle function, reduce fall risk, and indirectly lower stress‑fracture and osteoporotic injury risk in menopausal and perimenopausal women [60].
Clinical implications and future directions
Screening and monitoring bone health during menopause and perimenopause are critical to reducing fracture risk and preventing overuse injuries. DXA remains the gold standard for BMD assessment, typically performed at the lumbar spine and femoral neck [61]. Studies show that each standard deviation decrease in BMD at these sites increases fracture risk by 1.4 to 1.5 times, and women in the lowest quartile of spinal BMD face nearly three times the fracture risk compared with those in the highest quartile [62]. Independent predictors include: low BMD, history of prior fracture, smoking, multiple chronic illnesses, and non-use of hormone replacement therapy [35]. Risk stratification tools such as the FRAX algorithm combine femoral neck BMD with clinical risk factors like age, prior fracture, smoking, or glucocorticoid use to estimate the 10-year probability of a major osteoporotic fracture and guide decisions on screening and treatment [63]. Current guidelines recommend BMD screening for women younger than 65 with one or more risk factors, such as early menopause or low body weight. For women undergoing pharmacologic or hormonal treatments, repeat scans are advised every two to three years [64].
Advanced measures like TBS provide additional insight into bone microarchitecture, complementing BMD when fracture risk appears higher than density suggests [65]. Quantitative ultrasound and peripheral DXA may serve as preliminary tools but lack reliability for long-term monitoring [66]. Biomarkers of bone turnover can offer further predictive value in select cases. Early menopause, particularly before age 45, significantly elevates fracture risk (OR ~1.36 compared with menopause after age 45) [67], and population studies report an 8% incidence of fractures within three to four years among women aged 47–56, especially those with low BMD or prior fractures [68]. Interestingly, even women with relatively preserved BMD have reported stress fractures, suggesting that microarchitectural deterioration and biomechanical alterations also contribute [33]. Therefore, comprehensive screening using DXA, FRAX, and TBS, coupled with periodic monitoring and preventive strategies such as resistance exercise, adequate calcium and vitamin D intake, and fall-risk reduction, is essential for mitigating both fragility and stress fractures during the menopausal transition.
Advancements and future directions in managing menopausal structural strain and overuse injuries
Future directions in the prevention and management of overuse injuries and stress fractures in menopausal and perimenopausal women must move beyond general screening toward integrated, biomarker-guided interventions [69]. Recent advances in skeletal imaging, particularly high-resolution pQCT, allows for detailed microarchitectural analysis capable of detecting trabecular thinning and cortical porosity that are undetected by standard DXA. This technology allows for earlier identification of women at imminent risk of fracture [70]. The clinical utility of biochemical markers of bone turnover (e.g., serum C-terminal telopeptide of type I collagen [CTX] and procollagen type I N-terminal propeptide [P1NP]) is gaining ground for dynamic monitoring of bone response to mechanical loading and pharmacologic therapy, especially in those undergoing antiresorptive or anabolic treatment. Additionally, machine learning models trained on large datasets of postmenopausal athletes have begun to predict injury risk with high specificity by integrating hormonal profiles, gait mechanics, previous loading patterns, and genetic predispositions (e.g., polymorphisms in collagen type I alpha 1 [COL1A1] and estrogen receptor 1 [ESR1]) [71].
Research is also shifting toward mitochondrial and inflammatory signatures as intermediate biomarkers linking estrogen decline with impaired skeletal adaptation and tendon resilience. These developments indicate a need for multi-modal, sex-specific prevention protocols. Exercise prescription is expected to evolve into algorithm-based, periodized models that cycle intensity, impact, and recovery in accordance with individual hormonal responsiveness rather than arbitrary age stratification. Crucially, future strategies must embed preventive interventions before the onset of menopause, during perimenopausal transition when bone loss accelerates (2%–5% annually), and neuromuscular control declines. As such, menopause should be reframed not as a risk state but as a predictable, modifiable window where early intervention is anchored in mechanobiology, which can prevent structural failure. This shift requires increased funding for large-scale, longitudinal studies to validate early diagnostic thresholds and stratify risk across diverse populations [72,73].
CONCLUSION
The current literature supports a clear associated between menopausal changes and increases musculoskeletal vulnerability, including elevated risk of overuse injuries and stress fractures. Estrogen deficiency contributes to reductions in bone density, alterations in tendon structure, as well as declines in muscle mass and neuromuscular function. However, injury risk appears to arise from the interaction between these biological changes and mechanical loading patterns rather than hormonal factors alone. Critical gaps persist, including limited sex-specific exercise guidelines, underrepresentation of diverse populations, and a need for more longitudinal interventional data. Although hormone therapy demonstrates benefits for bone health in selected populations, its use requires an individualized risk-benefit assessment and should be considered in conjunction with non-pharmacological strategies.
Future research should focus on integrated models that combine hormonal, biochemical, and lifestyle factors to better define injury risk and optimize prevention strategies. Early screening, progressive load programs, and targeted exercise and nutrition interventions represent practical clinical approaches that can be implemented in preserving musculoskeletal health during menopausal transition.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
FUNDING INFORMATION
None.
AUTHOR CONTRIBUTION
Conceptualization: Ansari M, David S, Shopon M. Methodology: Hussain F, Ajmal H. Formal analysis: Ansari M, Hussain F, Asif M. Project administration: Ansari M. Visualization: Ansari M, Hussain F, Shopon M, David S. Writing – original draft: Ansari M, Hussain F, Ajmal H, Asif M. Writing – review and editing: Ansari M, Hussain F, Shopon M, David S. Approval of final manuscript: all authors.
DATA AVAILABILITY STATEMENT
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Table 1.
Hormonal and metabolic changes in menopause: musculoskeletal effects and preventive strategies
Adequate calories; protein; Ca/vitamin D; screen for RED-S/disordered eating
OPG, osteoprotegerin; DXA, dual-energy X-ray absorptiometry; TBS, trabecular bone score; CV, cardiovascular; BMD, bone mineral density; PT, physical therapy; RED-S, relative energy deficiency in sports.
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Adequate calories; protein; Ca/vitamin D; screen for RED-S/disordered eating
Table 1. Hormonal and metabolic changes in menopause: musculoskeletal effects and preventive strategies
OPG, osteoprotegerin; DXA, dual-energy X-ray absorptiometry; TBS, trabecular bone score; CV, cardiovascular; BMD, bone mineral density; PT, physical therapy; RED-S, relative energy deficiency in sports.
, Faisal Hussain, BS2
