Osteoporosis is the most common bone disease among the world’s population, affecting one in three women and one in five men over the age of 50. It can affect men and women of all ages since various factors such as genetics, nutrition, physical activity, and medications can contribute to its development, but it is most prevalent in postmenopausal women due to hormonal changes associated with menopause, which affect bone metabolism. In this article, we will explore the relationship between hormones and the development of osteoporosis, shedding light on how to identify and address hormone imbalances to optimize bone health.

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What is Osteoporosis? 

During childhood and adolescence, bones undergo a process called modeling, wherein new bone is added at one site while old bone is simultaneously from another site within the same bone. As individuals progress through their lifespan, this transitions into a process called remodeling. In remodeling, bone replacement and removal occur at the same location, resulting in a complete replacement of the skeleton approximately every 10 years. This intricate process requires collaboration between two types of cells: osteoblasts, cells that form bone, and osteoclasts, cells that break down bone. Not only genetics and environment, like physical activity and nutrition, contribute to bone health, but also the proper functioning of various systemic hormones. (30) 

Osteoporosis is a bone disease characterized by low bone mass and structural deterioration of the bone tissue that increases bone frailty and susceptibility to fractures. It is often asymptomatic, meaning individuals don’t know they have it until they experience a bone fracture. It is commonly diagnosed using dual-energy X-ray absorptiometry (DEXA), which uses X-rays at various sites prone to fracture, such as the hip and spine, to measure bone density. A bone mineral density (BMD) T-score of 2.5 or less indicates osteoporosis.

Factors that increase the risk of developing osteoporosis include excessive dieting, protein-restricted diets, diets low in calcium and vitamin D, certain medications like glucocorticoids, excessive alcohol intake, minimal physical activity, smoking, other medical conditions, aging, and hormone imbalances.

The Role of Hormones in Bone Health

The equilibrium between bone resorption and bone formation during bone remodeling requires balanced activity between osteoclasts and osteoblasts. Cytokines, such as IL-6 and TNFα, and hormones are two types of messengers that help to regulate their activity. (8)

Parathyroid

Parathyroid hormone (PTH) maintains calcium and phosphorus balance by acting on bone, kidneys, and the gastrointestinal tract. PTH regulates bone remodeling, acting on both osteoblasts and osteoclasts. It can stimulate both bone resorption and formation, depending on the dose and period of exposure. Continued exposure to PTH, as seen in hyperparathyroidism, has catabolic effects on the skeleton, increasing the risk of osteoporosis.

Thyroid

Thyroid-stimulating hormone (TSH) receptors are found on both osteoclast and osteoblast precursors. TSH inhibits the formation of osteoclasts and stimulates osteoblast differentiation. Hyperthyroidism can increase the risk of osteoporosis. (13)

Glucocorticoids

Glucocorticoids, exogenous or endogenous like cortisol, decrease new bone formation by inhibiting the formation and activity of osteoblasts by triggering apoptosis (cell death) and inhibiting the production of bone matrix proteins like collagen. (8)

Vitamin D

Vitamin D is a unique nutrient in that it is a vitamin that functions like a hormone. It supports osteoblast activity and regulates calcium absorption for bone mineralization. Research has shown that inadequate vitamin D intake over extended periods can cause bone demineralization. (8, 23)

Sex Hormones

Estrogen inhibits bone resorption by inhibiting osteoclast differentiation and modulating the release of inflammatory mediators, such as IL-6 and TNFα. Androgens, like testosterone, promote osteoblast differentiation in bone by inhibiting apoptosis and also suppress osteoclast proliferation. Progesterone plays a role in bone metabolism either by increasing bone formation through direct interaction with osteoblasts or by protecting against bone loss by preventing glucocorticoids from binding to osteoblasts.

Menopause, Hormonal Decline, and Bone Loss 

Aging affects bone remodeling in a sex-specific manner. In women, it is associated with increased bone reabsorption; in men, it is associated with decreased bone formation and turnover. Women are also more likely to develop osteoporosis than men, especially in the couple of years before menopause, with approximately 200 million women affected worldwide. (8, 42) These statistics and gender disparities highlight the important role the hormonal changes in menopause play in the development of osteoporosis.

Menopause is defined as the permanent cessation of menstruation (periods) for at least 12 consecutive months. It typically occurs from a decrease in ovarian follicles, resulting in significant hormone changes and marking the end of a woman’s reproductive years. Before the onset of menopause, women undergo a period of irregular menstrual activity and fluctuating hormones, referred to as the menopausal transition or perimenopause. The most significant hormone changes during this time include decreases in levels of inhibin B and anti-Mullerian hormone, increases in follicle-stimulating hormone (FSH), and fluctuations followed by low levels of estradiol and progesterone. This hormonal decline increases osteoporosis risk. 

During the menopausal transition, bone loss is accelerated due primarily to declining estrogen levels, with research showing up to 20% of bone density is lost in those first few years around menopause. There are two phases of bone loss in women. This first phase, related to menopausal hormone changes, leads to an increase in bone resorption. The second phase, which happens years after menopause, is attributed mainly to reduced bone formation, similar to general aging-related bone changes also seen in men. (21)

How to Test Hormones to Prevent or Treat Osteoporosis

Here are some useful tests for testing osteoporosis:

Thyroid Panel

Hyperthyroidism can increase the risk of osteoporosis. The Thyroid Panel by BostonHeart Diagnostics measures TSH, T4, T3, free T4, free T3, reverse T3, and thyroid antibodies to provide a comprehensive picture of thyroid function.

Adrenal Testing

The hypothalamic-pituitary-adrenal (HPA) axis releases hormones, like cortisol, in response to stress. Adrenal hormones can be measured using blood, saliva, and urine testing. The Cortisol test by BostonHeart Diagnstosics measures the total amount of cortisol in the blood, which is useful in diagnosing pathological conditions, such as Cushing’s syndrome, which can cause osteoporosis.

Genova’s Adrenal Stress Profile with Cortisol Awakening Response is a salivary test that measures the free or bioavailable amounts of cortisol. It uses multiple daily measurements to assess the diurnal rhythm of cortisol. It also measures the Cortisol Awakening Response (CAR), which can provide more information on how the body responds to stress. The DUTCH Adrenal test uses dried urine to assess for the daily free cortisol and cortisone patterns as well as the cortisol and cortisone metabolites. Measuring the metabolites reveals any issues with cortisol metabolism and clearance.

Sex Hormones

Sex hormones can also be measured using either blood, saliva, or urine testing. Precision Point’s Female Hormone Panel is a blood test measuring the primary reproductive hormones like luteinizing hormone (LH), FSH, estradiol, progesterone, and testosterone. Increasing levels of FSH, accompanied by lower levels of estradiol, can help to identify women entering perimenopause. The Female Salivary Profile I by ZRT Laboratories measures the free or bioavailable amounts of three reproductive hormones - estradiol, progesterone, and testosterone. Salivary testing can be instrumental in monitoring hormone levels during hormone replacement therapy (HRT). The DUTCH Sex Hormone Metabolites test measures estrogen, progesterone, and androgen hormones as well as their metabolites. It can be useful in assessing baseline hormones or monitoring levels during HRT.

Additional Tests

PTH and Vitamin-D-25-OH can be measured in blood tests to rule out hyperparathyroidism and vitamin D deficiency as risk factors contributing to osteoporosis.

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Prevention and Management Through Hormonal Balance 

Targeting hormones through lifestyle changes, supplements, and hormone replacement therapy can mitigate the adverse effects of menopausal hormonal changes on bone health.

Nutrition

A perimenopause-friendly diet includes plenty of fruits and vegetables, which contain dietary antioxidants, and plenty of plant-based protein sources. Oxidative stress, an overproduction of reactive oxygen species, contributes to ovarian aging and diminished estrogen production. Simultaneously, declining estrogen levels in menopause can reduce the body’s antioxidant capacities, exacerbating oxidative stress. Dietary antioxidants found in plant-based foods help to protect against ROS-mediated ovarian aging. Diets rich in plant-based protein sources have been shown to help slow down ovarian aging and prevent early menopause. Phytoestrogens are compounds that occur naturally in plant-based foods that have a similar chemical structure to estrogen and can interact with estrogen receptors. Some foods that contain phytoestrogens include non-GMO soy, broccoli, cauliflower, whole grains, peas, and flaxseeds. Research suggests that incorporating these foods into the diet can offer bone-sparing effects and help to reduce symptoms of menopause, like hot flashes, that occur due to fluctuating estrogen levels. 

The Mediterranean diet emphasizes fruits and vegetables, unprocessed whole grains, and healthy fats like olive oil while limiting processed foods, added sugar, and refined grains. Research suggests that adherence to this type of diet can delay the onset of menopause and that menopausal women who adhere to this diet experience improved mood, reduced vasomotor symptoms, reduced risk of all-cause mortality, and better bone mineral density. (14)

Physical Activity

Exercise regulates hormones, such as estrogen, parathyroid, and cortisol, as well as cytokines that impact bone metabolism. The mechanical force of exercise also helps to stimulate proper bone remodeling. Exercise has been recognized as an effective treatment strategy for menopausal bone loss. It seems that combining different types of exercise, such as resistance training with aerobic exercise, generates multiple types of mechanical forces on the bone at different loading sites to enhance overall effectiveness. 

Supplements

Below are several supplements that can support individuals with or at risk for developing osteoporosis:

Vitamin D

Vitamin D regulates calcium absorption and bone resorption. A large proportion of individuals do not meet their vitamin D requirements, and postmenopausal women, in particular, tend to have higher rates of vitamin D deficiency. Low vitamin D levels decrease calcium absorption, increasing osteoclast production and mobilization of calcium from bone. The National Osteoporosis Foundation recommends adults under age 50 get 400-800 IU of vitamin D daily, and adults over age 50 get 800-1000 IU daily. In cases of vitamin D deficiency, higher intakes might be required and should be discussed with your doctor. (38) Vitamin D3 increases the 25-hydroxy vitamin D level more efficiently than vitamin D2. 

Calcium

Calcium is an essential element in the human body, necessary not only for bone health but also for neuromuscular activity, blood clotting, and cardiac function. If the blood level of calcium is too low, bone resorption increases to draw stored calcium out into the bloodstream. The recommended daily intake of calcium for adults ages 18-50 is 1,000 mg and 1,200 mg for women over age 50. Studies evaluating the use of calcium and vitamin D supplementation in postmenopausal women saw reduced fracture risks with doses of 1,000-1,200mg daily. Supplements of both calcium carbonate and calcium citrate are used. Adults ages 19 through 50 should not exceed 2,500 mg total calcium intake daily, and adults over 50 should not exceed 2,000 mg total per day. Too much supplemental calcium increases the risk of kidney stones, constipation, and calcium build-up in the blood vessels. (38) 

Black Cohosh

Black cohosh, scientifically known as Cimicifuga racemosa, is a medicinal herb that contains phytoestrogens. It is used to treat menopausal symptoms, such as hot flashes and night sweats, and can also help to prevent menopause-related bone loss.

Maca

Maca, or Lepidium meyenii, is an adaptogen, meaning it helps the body to adapt more efficiently to stress and also contains phytoestrogens. In early postmenopausal women, it can help to balance cortisol levels, reduce menopausal symptoms, and increase bone density.

Hormone Replacement Therapy

Since estrogen deficiency is the primary underlying cause of menopausal bone loss, HRT is a possible treatment strategy for women before the age of 60 or within ten years of menopause. It can reduce the risk of fractures at all body sites and increase bone mineral density. (15, 43) Hormone replacement therapy can increase the risk of certain health issues like blood clots, strokes, breast cancer, and uterine cancer. Hormone replacement therapy should always be discussed with your doctor to determine if it is the right therapy for you or what delivery method should be used to minimize risks. (19)

Empowering Women: Knowledge and Proactive Measures 

Understanding personal risk factors and, in some cases, early screening is essential. The U.S. Preventive Services Task Force recommends osteoporosis screening for all women over age 65. Younger women should receive screening as early as 40 years old if they have factors that increase their chances of developing osteoporosis, such as: (20)

• Family history of osteoporosis
• Suffering fractures
• Low BMI
• Eating disorders
• Smoking
• Excessive alcohol consumption
• Insufficient calcium intake
• Vitamin D deficiency
• Low physical activity
• Health conditions like early menopause, rheumatoid arthritis, chronic kidney disease
• Corticosteroids
• Hormone therapies for prostate or breast cancer

Early detection of decreased bone density helps to prevent osteoporosis-related fractures that can cause disability and chronic pain and reduce quality of life. There are also lifestyle practices that women can implement to prevent bone loss as they age. Incorporating weight-bearing and resistance exercises, such as running, hiking, and weight lifting, three to four times weekly can help to stimulate healthy bone remodeling. Consuming adequate calcium and vitamin D is crucial for proper bone mineralization.

The daily recommended intake of calcium for women 50 and younger is 1,000mg, and for women 51 and older is 1,200mg. Calcium is found in foods like dairy, canned sardines and salmon (bone-in), collard greens, kale, okra, mustard greens, and broccoli. The daily recommended vitamin D intake is 600IU for women 70 and older and 800IU for women 71 and older. Vitamin D is found in fatty fish like salmon, dairy products, beef liver, and egg yolks. Adequate protein intake is also crucial for proper bone density. The recommended daily intake is 0.8 grams of protein per kilogram of body weight or 0.36 grams per pound. Quitting smoking and limiting alcohol can also protect bone density as we age. (27)

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Summary

Osteoporosis is a prevalent bone disease affecting millions of individuals worldwide. Multiple risk factors, such as dietary habits, lifestyle choices, medications, and hormonal imbalances, contribute to its development. The hormone changes during the menopausal transition accelerate bone loss, significantly increasing the risk of bone loss in menopausal women. Understanding the factors contributing to bone loss allows for proactive health changes to prevent unwanted bone changes later in life. Embracing hormonal health is an important part of this proactive, preventative approach to osteoporosis.