The Nexus between Nutrition, Bone Health, and COVID-19


Good nutrition plays a pivotal role in determining overall health and acts as a cornerstone in the prevention and management of chronic diseases. One aspect of health profoundly influenced by nutrition is bone health, which involves complex interactions at various levels, including bone metabolism, structural integrity, and density.

In this context, micronutrients such as vitamin D, calcium, fluorine, magnesium, potassium, vitamin B6, vitamin C, vitamin K, and zinc emerge as crucial contributors to optimal bone health.

This article delves into the multifaceted relationship between nutrition, bone health, and the impact of the COVID-19 pandemic on this intricate interplay.

Nutrition and Bone Health:

Beyond the well-established roles of vitamin D and calcium, a spectrum of micronutrients collaborates to fortify bone health. The intricate interplay involves influencing bone geometry, matrix mineralization, bone mineral density (BMD), and mitigating fall risks. Deficiencies in these micronutrients may elevate the risk of fragility fractures, emphasizing the importance of a comprehensive and balanced nutritional approach.

The Impact of COVID-19 on Lifestyle and Bone Health:

The COVID-19 pandemic has had far-reaching effects on global mental and physical well-being. Disruptions in lifestyle, characterized by reduced physical activity and unhealthy dietary habits, have become prevalent. Increased alcohol consumption and a rise in the intake of sugary foods have disrupted the delicate balance between caloric intake and energy expenditure. Prolonged lockdowns and sedentary lifestyles during the pandemic have raised concerns about compromised bone health, transcending age groups and escalating the risk of fragility fractures.

Biological Impact of COVID-19 on the Musculoskeletal System:

At a biological level, the SARS-CoV-2 virus has demonstrated a notable impact on the musculoskeletal system. The interaction between the virus and angiotensin-converting enzyme 2 (ACE2) holds key implications for bone homeostasis. ACE2, expressed not only in the lungs but also in bone marrow-derived stem/progenitor cells (BMSPCs), plays a crucial role in promoting skeletal repair through the ACE2/Ang-(1–7)/Mas axis. The downregulation of ACE2 induced by SARS-CoV-2 infection may disrupt this axis, potentially leading to bone fragility.

Inflammatory Factors and Bone Resorption in COVID-19:

The ‘cytokine storm’ and other inflammatory factors associated with COVID-19 contribute to the upregulation of receptor activator of nuclear factor-kappa B ligand (RANKL), increasing bone resorption. Ang-(1–7) emerges as a potential modulator, decreasing pro-inflammatory cytokines that play a direct role in bone resorption. The synergistic effect of ACE2 depletion and elevated cytokine levels in COVID-19 patients may induce osteoclastogenesis, further compromising bone health.

Oxidative Stress and Bone Remodeling in COVID-19:

Oxidative stress, amplified by the cytokine storm, coagulopathy, and cellular hypoxia in COVID-19, adds another layer of complexity to bone remodeling. Reactive oxygen species (ROS) regulation in osteoclast differentiation becomes pivotal, with physiological levels promoting osteoclast activity and higher concentrations, as seen in inflammatory states, leading to cell death and bone loss. Adequate nutrient intake, particularly vitamin D and zinc, assumes significance in bolstering the immune response, countering inflammation, and mitigating oxidative stress, thereby safeguarding bone health.

Hypoxemia, Acidosis, and Bone Homeostasis:

Severe COVID-19 cases, characterized by hypoxemia and subsequent acidosis, inhibit osteoprotective factors like osteoprotegerin (OPG). The disruption of bone homeostasis through upregulated RANKL and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), further underscores the potential risks to bone health during the pandemic.

Macronutrients and Micronutrients:

A balanced diet comprises macronutrients (proteins, lipids, and carbohydrates) and micronutrients (vitamins and minerals). Water, an essential component, constitutes 10–20% of bone volume, contributing to the integration of hydroxyapatite and collagen, thereby influencing the mechanical behavior of bone tissue.

Proteins, constituting about 50% of bone volume, influence bone health by positively affecting insulin-like growth factor-1 (IGF-1) production. Adequate protein intake supports osteoblast growth and differentiation. A positive association between animal protein intake and bone strength has been observed, emphasizing the quality of proteins for bone health.

Lipids, particularly saturated fatty acids (SFAs), can negatively impact bone health. High-fat diets have been linked to reduced bone mineral density (BMD), impaired microarchitecture, and increased fracture risk. Mechanisms include hyperinsulinemia, poor calcium absorption, increased retinol intake, and enhanced sclerostin expression.

Carbohydrates, specifically high intake of glucose and sucrose, have been associated with reduced BMD. The acidic environment created by high meat and cereal grain consumption may contribute to bone resorption. Conversely, fruits and vegetables, rich in water-soluble fibers, exhibit favorable effects on intestinal calcium absorption and BMD.

Micronutrients and Trace Elements: Calcium, stored in the skeleton as hydroxyapatite crystals, is crucial for bone strength. Adequate calcium intake, especially through dairy products and mineral waters, is essential to prevent bone remodeling and secondary hyperparathyroidism.

Fluoride, obtained from tea, seafood, and fruits, may enhance osteoblast activity and BMD, though conflicting results exist. Magnesium, present in nuts and leafy greens, modulates hydroxyapatite crystal formation in bone and influences osteoblasts and osteoclasts. Potassium, phosphorus, and B vitamins play protective roles in bone health, affecting bone remodeling and BMD.

Vitamins C, D, and K contribute significantly to bone health. Vitamin C supports collagen production and reduces the risk of hip fragility fractures. Vitamin D, obtained from sun exposure and certain foods, is vital for calcium metabolism and fracture risk reduction. Vitamin K promotes gamma-carboxylation of osteocalcin, enhancing bone mineralization.

Trace elements such as boron, copper, manganese, selenium, silicon (Si), strontium, and zinc play diverse roles in bone health. These elements regulate calcium excretion, remove bone free radicals, stimulate bone matrix formation, and influence osteoblast and osteoclast activity.

Table 1 – Benefits of nutrients on bone fragility in adults.

NutrientsDaily dietary reference intakesaBone metabolismParameters of bone strengthFragility fracture
Water (calcium- and bicarbonate-rich)2.7 (women) – 3.7 (men) LReduces serum PTH and CTXImprove ductility by integrating hydroxyapatite and collagenN/A
Proteins (particularly containing alanine, lysine, arginine, leucine, and glutamine)46 (women)–56 (men) gIncrease IGF-1 secretion, which enhances calcitriol synthesis leading to enhanced intestinal absorption of calcium and phosphate and kidney reabsorption of phosphate. Stimulate osteoblast growth and differentiation by enhancing insulin secretionContribute to type I collagen synthesis; increase periosteal circumference, cortical area, BMC, BMD, and strength-strain indexReduce hip fracture risk (−16%; observational study)
Lipids (i.e. MUFAs and α-linoleic acid)Not defined; 1.1 (women)–1.6 (men) g for α-linoleic acidN/AImprove trabecular and cortical volumetric BMDReduce hip fracture risk (−80%, observational study)
Carbohydrates (i.e. fruits and vegetables rich in water-soluble fibers containing inulin)130 gIncrease intestinal calcium absorption (+58%)Increase BMDN/A
Calcium (i.e. in dairy products and mineral waters)1–1.2 g99% stored in the skeletonForms hydroxyapatite crystals; improves BMDReduces the risk of fragility fractures (combined with vitamin D)
Fluoride3 (women)–4 (men) mgIncreases the procollagen propeptide type 1 N (P1NP)Improves spine BMDN/A
Magnesium310 (women)–420 (men) mg50% stored in bone to increase formation and size of hydroxyapatite crystals; increases osteoblast proliferation and vitamin D productionIncreases hip BMDReduces fracture risk (−62%; observational study)
Potassium2600 (women)–3400 (men) mgReduces NTXIncreases BMDN/A
Phosphorus700 mgStructural component of bones and teeth; modulates cartilage mineralization and osteoblasts activityIncreases BMDN/A
Vitamin B122.4 µgN/AIncreases spine BMD (only in patients with hyperhomocysteinemia)N/A
Vitamin C75 (women)–90 (men) mgStimulates the production of type 1 collagen by osteoblastsIncreases BMD at the spine and femoral neckReduces hip fracture risk (observational studies)
Vitamin D15–20 µgRegulates differentiation and mineralization of osteoblasts.
Increases the production of type 1 collagen and non-collagenous proteins (e.g. osteocalcin)
Increases the expression of RANKL in osteoblasts and inhibits the expression of OPG, stimulating osteoclastogenesis
Stimulates intestinal calcium absorption, and calcium and phosphate reabsorption in the kidneys, from the tubular fluid into the blood
Increases BMD and bone mineralizationReduces the risk of fragility fractures (combined with calcium)
Vitamin K90 (women)–120 (men) µgIncreases gamma-carboxylation of osteocalcinPromotes bone mineralizationReduces clinical fragility fractures
BoronN/AReduces calcium excretionImproves bone stiffnessN/A
Copper900 µgReduces osteoclasts resorptionN/AReduces hip fracture risk (observational study)
Manganese1.8 (women)–2.3 (men) mgN/AIncreases bone matrix formation and stimulates calcification. Increases BMDReduces fragility fracture risk (observational study)
Selenium55 µgReduces bone resorptionImproves bone microarchitecture (trabecular bone volume, trabecular number, and trabecular separation)Reduces fragility fracture risk (observational study)
Silicon25 mgIncreases osteoblast differentiation, and inhibits osteoclasts by reducing the RANKL/ OPG
Enhances alkaline phosphatase activity
Contributes to crosslinks between collagen and proteoglycans and to bone mineralization. Increases structural rigidity and quantity of force absorbed before breaking at the femurN/A
StrontiumN/AN/AIncreases bone volume and trabecular thickness, without affecting hydroxyapatite mineralizationReduces fragility fracture risk
Zinc8 (women)–11 (men) mgN/AN/AN/A

BMC: bone mineral content; BMD, bone mineral density; CTX, C-telopeptides; IGF, growth factor-1; N/A, not available; OPG, osteoprotegerin; PTH, parathyroid hormone; RANKL, receptor activator of nuclear factor-kappa B ligand; MUFA, monounsaturated fatty acid.

aDietary reference intakes according to the National Institutes of Health. Office of Dietary Supplements.

Risks of the Overintake of Micronutrients

While the benefits of sufficient micronutrient intake and supplementation are well-established, the potential risks associated with overconsumption, particularly concerning bone health, remain less explored. This chapter delves into the limited but crucial evidence surrounding the adverse effects of excessive micronutrient intake, emphasizing its implications for bone integrity.

Vitamin D Overdose: Vitamin D, essential for bone health, can lead to severe hypercalcemia and related symptoms like confusion, abdominal pain, vomiting, and dehydration in cases of vitamin D toxicity (VDT). Exogenous VDT, often caused by excessively high doses of pharmacological vitamin D preparations, is rare but can result in detrimental outcomes. Additionally, certain diseases, such as granulomatous disorders, can lead to endogenous VDT. These occurrences highlight the importance of cautious vitamin D supplementation to avoid adverse effects on bone and overall health.

Calcium Overconsumption: While evidence regarding the direct impact of calcium overintake on bone health is limited, excessive calcium supplementation has been associated with increased risks of cardiovascular diseases and malignancy. Studies, including meta-analyses, suggest up to a 30% higher risk of myocardial infarction and mortality, especially in men, due to calcium supplements. This underscores the need for a balanced approach to calcium intake, considering both dietary and supplemental sources.

Protein Excess and its Indirect Effects: An overconsumption of proteins has indirect effects on bone health. Excessive protein intake increases glomerular filtration rate and urinary calcium, potentially negatively impacting bone turnover. Increased urinary N-telopeptide excretion has been demonstrated, indicating disruptions in calcium balance. Careful consideration of protein intake is necessary to maintain a healthy balance and prevent adverse effects on bone tissue.

Negative Impact of Sugar Consumption: Sugar consumption, particularly from sugar-sweetened beverages, has been associated with negative effects on bone tissue, leading to low bone mineral density (BMD). Mechanisms involved include increased renal excretion of calcium and reduced intestinal calcium absorption, disrupting the balance between osteoblast and osteoclast activities and promoting bone resorption. These findings underscore the importance of dietary choices in maintaining bone health.

Vitamin A Overdose: Excess vitamin A intake has been linked to negative effects on bone health. Observational studies indicate that increased dietary retinol intake is associated with reduced BMD and an increased risk of hip fractures. Animal studies further highlight the suppressive effects of excessive vitamin A on bone mass gain, affecting cortical bone area, marrow area, endocortical perimeter, and periosteal perimeter. The active form of vitamin A, all-trans retinoic acid (ATRA), inhibits bone differentiation and mineralization, emphasizing the need for caution in vitamin A supplementation.

B Vitamins and Bone Health: Higher dosages of niacin (vitamin B3) have been associated with reduced bone strength, and clinical studies suggest a potential role in increasing the incidence of hip fractures in men with higher niacin intake. These findings prompt a closer examination of the impact of B vitamin supplementation on bone health, highlighting the need for judicious use.

Multivitamin Supplementation Considerations: The data presented raise important questions regarding the abuse of multivitamin supplementation, especially during the COVID-19 pandemic. The excessive intake of micronutrients, often without careful consideration of potential negative consequences, adds an additional risk factor for the occurrence of fragility fractures. Clinicians must be vigilant in evaluating the necessity and potential risks of micronutrient supplementation, emphasizing an individualized and evidence-based approach.

Bone Damage due to SARS-CoV-2 Infection

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection extends beyond respiratory manifestations, affecting various systems. In addition to pulmonary complications, COVID-19 exhibits extrapulmonary consequences, including neurological, gastrointestinal, and musculoskeletal complications, with persistent symptoms known as long COVID. This chapter explores the emerging evidence highlighting the contribution of SARS-CoV-2 to bone fragility and the potential long-term consequences on musculoskeletal health.

Long-COVID-19 and Nutritional Implications: Long-COVID-19, characterized by symptoms persisting for more than 12 weeks, presents challenges such as malnutrition, dysphagia, appetite loss, taste/smell alterations, gut microbiota changes, and sarcopenia. Adequate nutritional intervention becomes crucial, yet the bidirectional relationship between nutritional status and long-COVID-19 remains complex. Malnutrition and inadequate nutrition might contribute to the persistence of symptoms, emphasizing the need for a comprehensive nutritional approach in long-COVID-19 patients.

Bone Health in Severe COVID-19 Cases: Clinical data reveal that severe COVID-19 patients, especially those in intensive care, exhibit lower bone mineral density (BMD) compared to counterparts treated in other settings. Notably, spine BMD emerges as a predictor of mortality in this population. Despite the focus on cardiorespiratory and neurological complications during recovery, bone health is often neglected. The challenge lies in identifying COVID-19-related bone damage, particularly in older individuals with comorbidities, corticosteroid use, and immunosuppressive therapy.

Inflammatory Response and Bone Metabolism: Chronic inflammatory diseases, like chronic obstructive pulmonary disease (COPD), exhibit metabolic bone disorders, and COVID-19 shares inflammatory patterns impacting bone metabolism. The “cytokine storm” observed in severe cases enhances bone resorption, leading to persistent inflammation in bone marrow even after recovery. Animal models of SARS-CoV-2 infection demonstrate early and progressive trabecular bone loss, sustained by increased bone resorption and altered expression of osteoclast-related markers.

Effects of Immobilization and Medications: Severe COVID-19 cases often involve prolonged immobilization, sarcopenia, and medications like corticosteroids and anticoagulants, posing additional threats to bone health. Optimal nutritional intake becomes critical in intensive care, emphasizing the need for individualized approaches, especially considering deficiencies like vitamin D, which is associated with musculoskeletal disorders and poor outcomes.

Nutritional Habits During the Pandemic: The COVID-19 pandemic has triggered changes in lifestyle and nutritional habits. In low- and middle-income countries (LMICs), limited food intake during self-isolation contrasts with increased caloric intake, particularly in processed and nutritionally poor foods, in developed countries. Malnutrition risk rises in hospitalized COVID-19 patients globally.

Dietary Patterns and Alcohol Consumption: Increased snack consumption, especially at night, raises concerns about metabolic syndrome incidence. Studies report a shift towards foods of animal origin and canned foods, while fresh vegetable consumption decreases. Elevated alcohol consumption, linked to psychological disorders, emerges as a potential risk for fractures. Body weight gain during the pandemic, especially in individuals with higher BMI, further complicates dietary profiles.

Positive and Negative Dietary Trends: Positive trends include increased fruit and vegetable consumption in adolescents and home-cooked meals. However, some individuals report reduced intake of fresh vegetables, contributing to decreased potassium intake. Notable changes in dietary supplement use and purchase trends are observed, with implications for bone health requiring further investigation.

Impact on Bone Health and Micronutrient Deficiencies: Trace element deficiencies are noted in COVID-19 patients, raising questions about their potential role in bone health. While vitamin C supplementation during the pandemic is advised for immune support, its effects on bone health remain unclear. Vitamin D deficiency, exacerbated by changes in diet and limited sunlight exposure during quarantine, correlates with increased vertebral fragility fractures in COVID-19 patients.

Multivitamin Supplementation and Trace Elements: Observational studies suggest that multivitamin supplement users exhibit a lower risk of testing positive for SARS-CoV-2 infection. However, the effects of multivitamin administration on bone health in COVID-19 patients are yet to be investigated. Trace element assessment may aid in stratifying COVID-19 patients, but the direct impact on bone loss requires further research.

Conclusion: The multifaceted impact of SARS-CoV-2 infection extends to bone health, with implications for musculoskeletal integrity. Understanding the intricate interplay between viral infection, nutritional status, and bone metabolism is crucial for comprehensive patient care. This chapter emphasizes the need for tailored nutritional interventions and further research to elucidate the long-term consequences of COVID-19 on bone health.

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