Nutrition Research

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Summary

Osteoporosis is a major public health concern in many countries with increasing proportions of people surviving to an age where fractures are common. Osteoporosis is characterized by a degree of bone loss that makes bone fragile and more likely to break. The decline in sex hormone production is a major contributor to osteoporosis in both women and men, although bone loss occurs at a more rapid pace and at a younger age in women due to menopause. Therefore, women are at higher risk of osteoporosis and fracture at a younger age than men.

Condition Overview

Definition

The World Health Organization (WHO) defines osteoporosis as a condition characterized by the deterioration of bone micro-architectural structure and the loss of bone mass, leading to bone fragility and increased susceptibility to fracture (see Diagnosis).

Osteoporosis is primarily a disease affecting older adults. It rarely occurs in younger adults where it is usually associated with conditions like anorexia nervosa or long-term use of glucocorticoids.

Two types of bone loss occur with age:

  • Postmenopausal osteoporosis – linked to estrogen withdrawal and is especially significant in the decade that follows menopause in women
  • Age-related osteoporosis – associated with old age (>70 years old)
HIGHLIGHT I: POSTMENOPAUSAL BONE LOSS IN WOMEN

The rate of bone degradation starts to exceed the rate of bone formation in our thirties, leading to a loss of bone mass over time. At menopause, the dramatic decline in estrogen production by the ovaries initiates a phase of rapid bone loss that lasts for 4-8 years and leads to losses of 5-10% of cortical bone and 20-30% of trabecular bone. This period is followed by a phase with a slower rate of bone loss that lasts for the rest of life and contribute to losses of 20-25% of cortical and trabecular bone.

HIGHLIGHT II: POSTMENOPAUSAL BONE LOSS IN WOMEN

At menopause, estrogen withdrawal impairs calcium absorption in the intestine and reduces the kidneys’ ability to conserve calcium. As a consequence, calcium intakes fail to balance out the calcium that is lost in feces and urine, and blood calcium begins to fall. This triggers the secretion of the parathyroid hormone that stimulates bone resorption, which releases calcium into the circulation and offsets the negative calcium balance. However, this is done to the detriment of bone integrity: a negative balance of only 50-100 mg/day of calcium over a long period of time is thought to be sufficient to cause osteoporosis.

HIGHLIGHT: AGE-RELATED OSTEOPOROSIS

There is little difference in the timing of age-related osteoporosis between genders. Age-related bone loss and increased bone fragility are associated with reductions in physical activity and muscle strength that increase the risk of falling and breaking a bone. Moreover, age-related decline in the levels of steroid hormones — sex hormones and vitamin D — and in the activity of osteoblasts are also thought to contribute to age-related osteoporosis in both men and women. 

Prevalence in the US

Most recent estimates indicate that 43.4 million US adults have low bone mass (see Diagnosis), of which one-third are men and two-thirds are women.

Osteoporosis is also more common in women: an estimated 10.2 million US adults have osteoporosis, of which 8.2 million are women and 2 million are men (see Highlights: Postmenopausal Bone Loss in Women).

Diagnosis

Bone mineral density (BMD) at specific locations of the hip and spine is measured by dual-energy X-ray absorptiometry (DEXA) and compared to the standardized mean BMD of a healthy 30-year-old adult. This provides a T-score that is used for diagnostic purposes. Clinically, a T-score of -2.5 standard deviations (SD) or below gives a diagnosis of osteoporosis in postmenopausal women and men aged ≥50 years (Table 1).

Table 1. T-score Cutoffs Defined by the World Health Organization
Normal bone mass T-score equal to or above -1 standard deviation (SD)
Low bone mass (osteopenia) T-score between -1 SD and -2.5 SD
Osteoporosis T-score equal to or below -2.5 SD

Risk of Fracture

The burden of osteoporosis lies primarily in the fractures that arise. Osteoporotic fractures are often precipitated by falls from standing height, although vertebral fractures can occur in the absence of a fall during daily, routine activities. Osteoporosis causes 2 million fractures each year in the US and costs ~20 billion dollars annually. About 70% of osteoporotic fractures affect women. Worldwide, 1 in 3 women and 1 in 5 men aged >50 years will suffer from a fracture.

The risk of osteoporotic fracture is influenced by bone mass, bone structure (microarchitecture, geometry), and propensity to fall (balance, mobility, muscular strength). The Fracture Risk Assessment Tool (FRAX) is an online tool that helps estimate one’s probability of fracture over the next 10 years, taking BMD measurement and additional risk factors into account (Table 2).

Table 2. Risk Factors Considered to Estimate the 10-year Fracture Risk Probability with the FRAX Tool
Age (between 40 and 90 years)
Sex
Weight and height
Previous osteoporotic fracture
Parental history of hip fracture
Current tobacco smoking
Use of glucocorticoids (>3 months of doses equivalent to 5 mg/day of prednisolone)
Confirmed diagnosis of rheumatoid arthritis
Conditions associated with secondary osteoporosis (type 1 diabetes mellitus, osteogenesis imperfecta, untreated long-standing hyperparathyroidism, hypogonadism or premature menopause [<45 years], chronic malnutrition, or malabsorption and chronic liver disease)
Alcohol intake: ≥3 units (drinks)/day
Low femoral neck BMD

Fracture-related Morbidity and Mortality

Osteoporotic fractures often lead to a reduced quality of life and premature death. Hip fractures are the most serious of all osteoporotic fractures since 12-20% of women suffering from a hip fracture die during the following 2 years, and 50% of those surviving lose their independence and require long-term nursing care. The risk of death after hip fracture is higher in men than women. Fractures at other sites can also be debilitating. Multiple and/or severe vertebral fractures can lead to loss of height and abnormal bending of the upper and middle back (thoracic spine), reducing lung function and affecting digestion. Vertebral and non-hip, non-vertebral fractures are also associated with premature mortality.

DEFINITIONS
Anorexia nervosa - a serious disorder in eating behavior characterized by self-imposed starvation causing severe malnutrition and excessive weight loss
Bone mineral density (BMD) - the quantity of mineral present per given area/volume of bone, is a surrogate for bone strength
Bone resorption - the breaking down of bone by specialized cells (osteoclasts)
Cortical bone - the type of bone that makes me the outer shell of the skeleton
Glucocorticoids - a type of steroid hormones, naturally produced by the adrenal glands (located on top of the kidneys). Long-term use may impair calcium absorption as well as bone formation, and precipitate osteoporosis
Menopause - describes the period of a woman’s life when menstruation ceases
Osteoblasts - cells involved in making bone
Parathyroid hormone (PTH) - hormone secreted by the parathyroid glands.
Sex hormones - a type of steroids that are released by specific tissues - primarily adrenal glands, ovaries, and testes – and govern sexual development and reproduction; e.g., estrogen, testosterone
Trabecular bone - the type of bone that fills the end of the limb bone and the vertebral bodies in the spine 

References:

  • Pettifor JM, Prentice A, Ward K, Cleaton-Jones P. The skeletal system. Nutrition and Metabolism. 2nd ed. Wiley-Blackwell; 2016:272-311.
  • Alswat KA. Gender disparities in osteoporosis. J Clin Med Res. 2017; 9(5):382-387.

For more information:

Nutrition Research

Protein-energy Malnutrition (PEM)

What it is

General

  • PEM is caused by deficiencies in macronutrients. Severe forms are known as marasmus (due to severe restrictions in all sources of energy intake) and kwashiorkor (due to severe restrictions in dietary protein).
  • PEM is most common in developing nations, the elderly, hospitalized individuals, and those with chronic diseases that interfere with nutrient absorption and utilization. In Western countries, marasmus-type PEM is usually observed in elderly people in the community or in long-term care, whereas low-albumin PEM is found in hospitalized patients.

Bone-specific

  • In older adults, PEM may compromise many aspects of health, leading to falls and fracture.
What we know
  • Higher protein intakes are associated with greater bone mass density and lower risk of fracture.
  • Higher protein intakes are likely to be protective unless calcium intakes are inadequate, in which case higher protein intakes may be harmful.
  • Protein supplementation after bone fracture limits bone loss and reduces serious complications, including death.
DEFINITIONS
Albumin - a major blood protein. It contributes to regulate blood volume (through "colloid osmotic pressure") and transports various molecules (fatty acids, metals, ions, hormones, etc.) in the circulation
Low-albumin protein-energy malnutrition (PEM) - laboratory diagnosis of marginal PEM usually includes measures of serum albumin. However, albumin is not a specific indicator of PEM as its concentration in blood is altered in many conditions other than PEM

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Calcium

What it does

General

  • Calcium plays an essential role in cell-signaling pathways and is therefore fundamental to virtually all physiological functions.

Bone-specific

  • Calcium is a major structural component of bones.
  • Low calcium intakes may increase the risk of osteoporosis and fracture.
  • The substitution of ultra-processed foods and soft drinks for unprocessed meals, milk, and other calcium-rich food is likely to damage bone health over the long run.
What we know
  • Calcium supplementation is not effective to prevent postmenopausal and age-related bone loss; calcium can only limit bone loss in the first 1-2 years of supplementation.
  • There is no consensus regarding calcium and vitamin D supplementation for the primary prevention of fractures in community-dwelling older adults (see Table 3).
  • The benefit of supplemental calcium (and vitamin D) on fracture risk might be restricted to people with known osteoporosis, those with low vitamin D status, and the institutionalized elderly.
  • Calcium intake from food is preferred over supplements, and total intakes should not exceed 2,000 mg/day in adults >50 years.
Table 3. Recommendations Regarding Calcium and Vitamin D Supplementation for Older Adults
Foundation/Society/Task Force Recommendations to Reduce the Burden of Fractures
[US] Bone Health & Osteoporosis Foundation
  • supports the use of supplemental calcium (1,000-1,200 mg/day) and vitamin D (800-1,000 international units [IU]/day) to reduce the risk of fracture in all middle-aged adults (2016)
[US] American Geriatrics Society
  • supports the use of supplemental vitamin D (1,000 IU/day) with calcium in all community-dwelling, older adults (≥65 years) and in older adults under institutionalized care to reduce the risks of fall and fracture (2014)
US Preventive Services Task Force
  • advises against daily calcium and vitamin D supplementation for the primary prevention of fracture in community-dwelling, postmenopausal women (2013)
  • advises against the use of supplemental vitamin D to prevent falls in community-dwelling older adults (≥65 years) without osteoporosis (2018)
DEFINITIONS
Cell-signaling pathway - a cascade of events triggers by a signal outside a cell and resulting in a functional change inside the cell. Cell-signaling pathways play important roles in regulating numerous cellular functions in response to changes in a cell’s environment. Also refers to as cell-transduction pathways or signaling cascades
Primary prevention - refers to a range of activities undertaken to prevent or reduce the risk of an injury or disease before it occurs
HIGHLIGHT:
Use the International Osteoporosis Foundation’s Calcium Calculator to find out whether you are getting enough calcium.

For references and more information:

Calcium Flashcard. Main Functions: 1) structural component of bones and teeth, 2) regulates nerve transmission and muscle contraction, 3) helps maintain a healthy blood pressure, and 4) helps maintain acid-base balance in the blood. Good Sources: dairy (yogurt, milk, cheese), plain yogurt, 8 ounces or 1 cup = 415 mg; sardines (canned) 1 can or 3.75 ounces = 351 mg; green leafy vegetables (kale, bok choy), collard greens (cooked), one-half cup = 300 mg; mg= milligrams. Daily Recommendation: 1,000 mg for men 19-70 years, 1,200 mg for men 71+ years; 1,000 mg for women 19-50 years, 1,200 mg for women 51+ years. Special Notes: 1) Many Americans do not consume enough calcium. Just 3 servings of dairy per day would meet the recommendation. For those who don't consume dairy, calcium-fortified juices, cereals, and milk alternatives are a good substitute. 2) To maximize absorption from supplements, take no more than 500 mg at a time.

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Fluoride

What it does

General

  • Fluoride-containing dental products and adequate intakes of fluoride reduce the occurrence of caries throughout life by promoting tooth mineralization.

Bone-specific

  • Fluoride increases the structural stability of bones through interacting with calcium phosphate salts.
What we know
  • The level of exposure achieved through community water fluoridation (<3.4 mg/day) is unlikely to be helpful in the prevention of osteoporosis and fracture.
  • Trials found that supplementation with daily doses ≤20 mg of fluoride reduced the risk of fracture.
    • The US FDA does not currently approve the use of fluoride supplementation in the prevention and treatment of osteoporosis.
DEFINITIONS
Caries - cavities or holes in the outer layer of a tooth — the enamel and dentin
Community water fluoridation - refers to the controlled addition of fluoride to water as a public health measure to decrease the incidence of dental caries
FDAUS Food and Drug Administration
Tooth mineralization - the process by which calcium and phosphorus are deposited into dentin and enamel

For references and more information, see the section on Fluoride in the in-depth article on Bone Health.

Fluoride Flashcard. Main Functions: (1) Structural component of bones and teeth, and (2) Prevents cavidties by (a) promoting tooth mineralizations and (b) inhibiting the activity of acid-producing bacteria that cause tooth decay. Good Sources: water (fluoridated water, 1 cup or 8 ounces = 0.2-0.3 milligrams) and tea (black tea, 1 cup or 8 ounces = 0.2-0.5 mg). Daily Recommendation: 4 mg for men and 3 mg for women. Special Notes: (1) Dental products are also a source of fluoride and (2) Claims that fluoride increases the risk of several chronic diseases are not supported by extensive scientific research.

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Phosphorus

What it does

General

  • Phosphorus is an essential structural component of cell membranes and chromosomes and is involved in many biological processes, including bone mineralization.

Bone-specific

  • Phosphorus and calcium form insoluble hydroxyapatite crystals that give bones their rigidity.
What we know
  • Current intakes of phosphorus in the US population are well above the EAR (580 mg/day) and RDA (700 mg/day), with daily estimates of 1,602 mg/day in men and 1,128 mg/day in women. Yet, intakes of phosphorus currently experienced in the US have not been associated with a higher risk of osteoporosis.
DEFINITIONS

Bone mineralization - the process by which calcium and phosphorus are laid on the organic bone matrix
EAR - estimated average requirement. It is the nutrient intake value that is estimated to meet the requirement of 50% of the healthy people of a particular gender and age group in a population. It is also the best estimate of an individual’s requirement and thus may be used to assess the adequacy of an individual’s usual intake of the nutrient
Hydroxyapatite crystals - calcium phosphate salts forming crystals ((Ca)10(PO4)6(OH)2) that constitutes the main mineral in teeth and bones
RDA - recommended dietary allowance. It is the nutrient intake value that is estimated to meet the requirement of nearly all healthy people of a particular gender and age group in a population. It is a target value for an individual

For references and more information:

Phosphorus Flashcard. Main Functions: (1) Structural component of bones and teeth, DNA and RNA, and cell membranes; (2) Assists in energy production and storage; and (3) Physiological buffer. Good Sources: dairy products (yogurt, plan, nonfat, 8 ounces, 306 milligrams [mg]); meat (beef, poultry, fish), cooked salmon, 3 ounces, 315 mg; egg, 1 large, 86 mg. Daily Recommendation, 700 mg for all adults. Special Notes: (1) Phosphorus deficiency is very uncommon and usually only observed in cases of near-total starvation or in rare, inherited kidney disorders. (2) High blood phosphorus concentration is linked to increased risks of cardiovascular disease and death. (3) The subsitution of phosphate-containing soft drinks and snack foods for milk and other calcium-rich food may compromise bone health.

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Vitamin D

What it does

General

  • Vitamin D is made in the skin upon sunlight (UV) exposure and is also obtained from a few foods or from supplements.

Bone-specific

  • When dietary calcium intakes are low, vitamin D stimulates the release of calcium from bone.
What we know
  • Older people are at increased risks of poor vitamin D status (serum 25-hydroxyvitamin D values between 12-20 ng/mL) and skeletal disorders due to less sun exposure, a lower capacity for vitamin D synthesis, and reduced dairy intake.
  • Current evidence suggests no effect of vitamin D supplementation alone on fracture risk.
  • Vitamin D supplementation may contribute to reduce the risk of fall in adults ≥65 years.
DEFINITIONS

Serum 25-hydroxyvitamin D - a reliable measure of vitamin D status

For references and more information:

Vitamin D (calciferol) Flashcard. Main Functions: 1) Facilitates absorption of calcium and phosphorus, 2) Promotes bone health, 3) Required for proper immune function, and 4) Influences cell growth and development. Good Sources: Fatty Fish (salmon, mackerel, sardines), pink canned salmon, 3 ounces = 465 IU or 11.6 micrograms; Canned mackerel, 3 ounces = 211 IU for 5.3 micrograms; Fortified food, low-fat milk, vitamin D fortified, 8 ounces = 98 IU or 2.5 micrograms. Daily Recommendation: 600-1,000 IU (15-25 micrograms) for chldren and adolesents (4-18 years), because vitamin D is scarcely found in food, it may be necessary to take supplements. 2,000 IU or 50 micrograms for all adults, this amount applies to supplemental vitamin D, which is recommended in addition to vitamin D from a mixed diet. Special Notes: 1) The Daily Recommendation listed is specific to the LPI based on extensive review of the scientific evidence. The Institute of Medicine's Recommended Dietary Allowance (RDA) is 600 IU (15 micrograms)/day for males and females who are 4-70 years old, and 800 IU (20 micrograms)/day for all adults over 70. 2) Vitamin D is considered a "Nutrient of Public Health Concern" because underconsumption is linked to adverse health outcomes. 3) More than 90% of Americans do not meet the dietary requirement for vitamin D. 4) our bodies make vitamin D upon skin exposure to UVB radiation from the sun. Darker skin color, northern latitude, and older age impede the amount of vitamin D produced.

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Other Nutrients

  • Excess sodium can be harmful to bone health in older women especially when they have suboptimal calcium intakes. Adopting a diet that increases potassium intake and reduces sodium intake (i.e., high in fruit, vegetables, and dairy, and low in meat) might help support bone health.
  • Several additional micronutrients have essential roles in supporting and maintaining bone health (magnesium; vitamins A, B, C, and K). Yet, there is no evidence that supplementation at levels above current recommendations may be of benefit regarding the prevention of osteoporosis and fracture. Note that the US Bone Health & Osteoporosis Foundation advises against the use of vitamin K supplements in people at risk for blood clots and in those taking blood-thinning medications.

For references and more information:

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Alcoholic Beverages

  • Light drinking may not be harmful to bone health. However, higher intakes of alcohol (≥4 drinks/day) increase the risk of fracture.

 

Physical Activity

  • Regular physical activity, especially weight-bearing exercise, is associated with less age-related bone loss over time and with a lower risk of fracture.
    • However, there is no evidence that even high-intensity exercises can limit bone loss due to menopause.
  • Exercising may be detrimental to bone health if the body does not receive the nutrients it needs to remodel bone tissue in response to impact and tension forces generated by physical activity.
  • Physical activity is highly beneficial across all stages of bone development. Even frail elderly people should remain as physically active as possible to preserve bone health.
DEFINITIONS
Menopause - describes the period of a woman’s life when menstruation ceases

For references and more information, see the section on Lifestyle factors in the in-depth article on Bone Health.

 

Smoking

  • Smoking is associated with a higher risk of fracture and slower recovery from fracture.
  • Smoking cessation reverses (at least partially) the increase in risk of fracture reported in smokers compared to non-smokers.

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The writing of this content was supported by a grant from Pfizer Inc.