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How Hormones Affect Bone Health

 

  • Hormones control all aspects of your health, including whether your bones are strong or decaying and getting weaker.
  • Estrogen, testosterone, thyroid hormone, oxytocin, serotonin, melatonin, and cortisol all affect your bones.
  • Maintaining healthy hormone levels prevents and reverses osteoporosis.
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By Dr. John Neustadt

Hormones control all aspects of your health, including your mood, metabolism, sleep, digestion, bone health, and, if you’re a woman, your menstrual cycle. You produce about 50 different hormones. Most people know that estrogen is important for bone health, but so are other hormones. This article reviews how some of these chemicals—estrogen, testosterone, thyroid hormone, oxytocin, serotonin, melatonin, and cortisol—affect your bones.

Estrogen

Estrogen helps bones by activating genes that increase bone formation and collagen production, decrease bone loss, and reduce inflammation.1 Estrogen is so important for bone health that the greatest decrease in bone density occurs when estrogen declines with menopause and for the ten years after.2  

How Estrogen Affects Bone

Estrogen has many positive effects on bone. It increases insulin-like growth factor 1 (IGF-1), which enhances bone-building osteoblast activity and collagen production.3 Collagen is the most abundant protein in your body and a critical building block for the matrix of molecules that support cells, connective tissue, organs, and bones. It’s found in your skin, hair, and nails. Collagen comprises 90% of the organic matrix of bone, and estrogen stimulates collagen production.4,5 Collagen is so strong that even the smallest building blocks of collagen are five to ten times stronger than steel.6 When you produce less collagen, bone becomes brittle and weak, and your skin thins, wrinkles, and sags. 

While estrogen enhances molecules that stimulate bone production, it also decreases other chemicals that destroy bone. This includes nuclear factor-kappa beta ligand (RANKL) and sclerostin.7 RANKL and sclerostin enhance bone-destroying osteoclast activity. Thus, when you reduce RANKL and sclerostin, more bone is created.  

These molecules have been so well studied that two medications, denosumab (Prolia) and romosozumab (Evenity), were developed that decrease RANKL and sclerostin, respectively. Your own estrogen naturally does this as one of the ways it creates new, healthy bone.8,9 

Estrogen also helps balance inflammation by decreasing proinflammatory molecules. Chronic inflammation damages bones and speeds up the aging process. When estrogen declines, molecules that create inflammation increase, including interleukins 1 and 6 (IL-1 and IL-6) and tumor necrosis factor-alpha (TNF-alpha). Estrogen’s ability to improve bone health is partly due to reducing inflammation.10 

Hormone Replacement Therapy

Estrogen replacement increases bone mineral density (BMD) and reduces fractures. Women in the National Osteoporosis Risk Assessment (NORA) taking hormone replacement therapy had a 40% lower risk of hip fractures compared to women who had never used hormone replacement therapy.11  

In a meta-analysis of 28 studies with 33,426 women, the use of menopausal hormone replacement therapy was associated with a 26% reduction in overall fracture risk, 28% lower hip fracture risk, and 37% lower vertebral fracture risk. Importantly, in their analysis, the researchers determined that the bone-protective effects of hormone replacement may decrease after someone stops it or when started after the age of 60.12 

Estrogen can also be combined with progesterone. Progesterone also has bone-building effects, and the combination has been shown to reduce fractures in postmenopausal women with osteoporosis.13 

Estrogen Safety

The safety of estrogen replacement therapy, or estrogen plus progesterone, depends on the type, dose, and duration of the replacement, as well as a woman’s individual risk profile. How it’s taken (e.g., orally or as a cream) also can have an impact on safety. If menopausal hormone replacement therapy is something you want to pursue, talk to your healthcare provider about whether this is a good option. 

Testosterone

Testosterone is important for cardiovascular health, mood, sex drive, cognition, bone health, and more. While it’s well-known as a male hormone, women also produce small amounts of testosterone. Low testosterone can cause osteoporosis and should be tested in men with osteoporosis.   

As boys grow and their bones mature, testosterone creates thicker, stronger bones, resulting in larger bones in men than in women.14 In addition to testosterone’s direct actions on bone, it also converts to a type of estrogen called estradiol (E2). Once peak bone mass is achieved between twenty-five and thirty years old, maintaining strong, healthy bones in aging men is largely due to its conversion to estradiol.15 Reduced serum estradiol is an independent risk factor for fractures in men, and men with the combination of low testosterone and low estradiol are at a greater risk for bone loss and fractures.16 

Guidelines for managing bone health in men with low testosterone have been developed, with the approach being to bring testosterone back into a normal range. 

Thyroid Hormone

The thyroid is a butterfly-shaped gland at the base of the neck that produces two hormones, levothyroxine (T4) and triiodothyronine (T3). About 80% of thyroid hormones produced are T4 and about 20% are T3. T4 is inactive and is converted in tissues throughout the body into the active T3 hormone.  

These chemical messengers regulate metabolism in every cell in the body, affecting your bones, blood, digestion, mood, memory, hair, and energy. The production and release of T4 and T3 are controlled by thyroid-stimulating hormone (TSH), which comes from the pituitary gland in the brain. 

Thyroid receptors in the skeleton regulate bone and cartilage production.17 Hypothyroidism in children can reduce bone growth and result in short stature. In adults, hypothyroidism reduces osteoblast activity, resulting in less bone formation, but there is currently no clear data demonstrating a relationship between adult hypothyroidism and decreased bone mineral density.18 

In contrast, hyperthyroidism disrupts the balance between osteoblast and osteoclast activity, resulting in more osteoclast-induced bone breakdown and bone loss.18 It’s common knowledge among clinicians that this situation damages bones, causes osteoporosis, and increases fracture risk. It also creates rapid heart rate (tachycardia), irregular heartbeats (arrhythmia), heart failure, anxiety, excessive sweating, heat intolerance, unintentional weight loss, and is associated with increased mortality.19, 20

However, many clinicians don’t know that subclinical hyperthyroidism, which causes milder symptoms, also increases the risk of osteoporosis and fractures. The difference between these diagnoses comes down to the TSH, T4, and T3 test results. In both conditions, TSH is low. However, T4 and T3 are elevated in hyperthyroidism but normal in subclinical hyperthyroidism. 

In a meta-analysis of 13 studies with more than 70,000 volunteers followed for 12 years, researchers concluded that subclinical hyperthyroidism is associated with up to 61% increased risk for hip fractures and up to 98% increased risk for any fracture compared to people with normal thyroid function. The lower the TSH, the greater the risk.21 

Oxytocin

Oxytocin is a small hormone produced by the hypothalamus in the brain. It then goes to the posterior pituitary gland, where it’s released into the bloodstream. Oxytocin is your bonding and safety hormone. It’s what fosters the bond between mother and child, helps you feel connected with others, and builds social trust and alliances. When you’re supported in a relationship, oxytocin is flowing.  

Beyond being one of your happy chemicals that helps you feel good, research suggests that living your life in ways that promote healthy levels of oxytocin may help you live longer. In a groundbreaking study in 1966, researchers showed that animals that received injections of oxytocin lived significantly longer than those who didn’t.22 

Oxytocin was first discovered in the early 1900s and synthesized in 1953.23 But it wasn’t until decades later—in the late 1990s—that researchers identified oxytocin receptors on bone cells, first on osteoblasts, then also on osteoclasts.24,25 This brain-bone connection opened a new area of research and understanding about bone physiology and health. Interestingly, while bone cells can get oxytocin that reaches them through the bloodstream, osteoblasts manufacture their own oxytocin.26  

Oxytocin Clinical Trials

Clinical trials haven’t been conducted to determine whether treating patients with oxytocin improves bone density and reduces fracture risk, but animal research repeatedly concluded that oxytocin builds stronger bones.27-29 Additionally, studies have consistently shown an association between oxytocin and bone density. In one study, oxytocin was 55% lower in women with postmenopausal osteoporosis compared to women without osteoporosis.30 Another study with more than 1000 postmenopausal women concluded that higher oxytocin levels are associated with higher bone density.31 

Living your life in ways that boost oxytocin may help preserve bone and reduce your risk of dying. People who are social had an up to 30% lower risk of dying from heart disease, stroke, diabetes, Alzheimer’s, and all-cause mortality.32 While the study didn’t specifically look at death from osteoporosis, a 30% drop in death from any cause includes all diseases. Had they specifically evaluated death from osteoporosis, however, I suspect the results would have been similar since other research concluded that poor social support is associated with a faster loss of hip BMD and worse recovery from hip fractures.33, 34 While the researchers didn’t measure oxytocin, social interactions boost oxytocin, and that may explain why social interactions are so beneficial.  

Fortunately, there are many things you can do to naturally boost oxytocin that can help you feel more grounded, calmer, and connected. It can also help protect your bones. 

Serotonin

You’ve likely heard of serotonin as one of your happy chemicals. Entire classes of medications have been developed that artificially increase serotonin as a treatment for depression. And they’re wildly popular. Almost 14% of all US adults took antidepressants in 2018, and that was before the pandemic turned everyone’s world upside down. Like with so many other things, the older people get, the greater the risk for depression. Nearly 25% of all women 60 years old and older took an antidepressant in 2018.35  

But most of your serotonin isn’t produced in the brain. Cells in your intestines create 95% of your body’s serotonin, which never enters the brain. Instead, nearly all of the gut-derived serotonin is concentrated in platelets that circulate through your blood vessels.36 All of those cells and their benefits are only possible because your bones create them.  

Serotonin affects bone health by binding to serotonin receptors on osteoblasts and osteoclasts.37, 38 When serotonin is at natural, healthy levels, it the balance of osteoblast and osteoclast activity is maintained to support strong, healthy bone. However, when serotonin increases, which is what happens when someone takes a medication that artificially boosts serotonin, the hormone becomes unhealthy. In these situations, elevated serotonin inhibits osteoblasts, so less bone is created, and more bone is destroyed.36 

In a Canadian study that tracked patients for 10 years, the researchers found that taking either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) was associated with a 68% increase in fracture risk.39 Another study found that women taking SSRIs were losing bone more than 1.6 times faster than women who weren’t on those meds.40

Two studies evaluated how many patients would have to take SSRIs before one of them experienced a fracture. One of the studies determined your gender or age didn’t matter; the fracture risk was the same.41 For every 42 patients taking an SSRI, we can expect one of them will break their hip, wrist, or forearm. 

The researchers working on the second study evaluated their data a little differently. They looked at the risk for fractures based on how long someone took the medicine. They found that even taking an SSRI for just a year or less still increased someone’s fracture risk so much that for every 85 patients taking the medication, they’d expect one of them to break a bone. 

It got even worse the longer someone took the drug. For every 19 patients taking the antidepressant for one to five years, one of them would be expected to break a bone.42 This is extremely alarming since nearly 25 million adults have been on antidepressants for more than two years. Another 15.5 million have been on the medications for at least five years, and many people find it extremely difficult to discontinue these medications because of the side effects they experience when they try to do so.43  

Most people, including doctors, aren’t aware that serotonin has powerful effects on bones. When people artificially increase their serotonin with these drugs, it indirectly damages bone by altering the nervous system, which increases the activity of bone-destroying osteoclasts. And they directly damage bones by decreasing the activity of bone-building osteoblasts. With a natural balance of serotonin, you get strong bones because the effects of bone-destroying osteoclasts are offset by osteoblasts. But these medications throw off that delicate balance, which damages bones, causes osteoporosis, and creates fractures. 

Melatonin

You’ve likely heard of melatonin for sleep. It’s produced by the pineal gland in the brain and helps you fall asleep. But just like serotonin, melatonin isn’t only produced in the brain. Bone cells create melatonin and recent research has revealed melatonin regulates bone health.44 Melatonin stimulates osteoblasts to create new bone. 

The hypothesis that melatonin might be helpful in people with osteoporosis was tested in a 2015 study with 81 postmenopausal women with osteopenia.45 This placebo-controlled, randomized clinical trial had women taking one mg of melatonin, three mg of melatonin, or a placebo at bedtime for one year. After one year, they found that BMD significantly increased in women taking both one mg and three mg of melatonin, with the higher dose providing greater benefit. In women taking three mg of melatonin, femoral neck BMD increased by 2.3%, and the spine BMD increased by 3.6%. However, BMD did not increase at any other sites (e.g., the forearms or wrists). Additionally, the researchers did not evaluate whether taking melatonin also reduced fracture risk. Hopefully, future research will test melatonin in people with osteoporosis and, most importantly, evaluate whether melatonin reduces fractures.  

Cortisol

Cortisol is released by the adrenal glands during stress. Over the short term, the stress response is adaptive. It helps us handle things better, enhances immune function, and helps us focus. However, long-term stress has the opposite effect. It’s linked to lowered immune function, elevated blood pressure, and increased heart rate.46 Chronic stress also contributes to insomnia, heart disease, dementialeaky gut, dysbiosis, osteoporosis, sagging skin, and arthritis. And it literally shrinks your brain.47-49 

We’ve known for decades that high cortisol levels create osteoporosis. Medications that artificially elevate cortisol, like prednisone and dexamethasone, increase osteoporosis and fracture risk by up to 200%. But your body’s own production of cortisol can destroy bone too. Cushing’s disease is a medical condition in which the adrenal glands produce too much cortisol and is a secondary cause of osteoporosis. Someone with this disease could have cortisol levels four to five times higher than normal. However, studies have shown that even in “normal, healthy” men and women, having cortisol that is toward the higher end of normal is a risk for losing bone faster.50, 51  

Chronic stress strips calcium from bone and increases fracture risk by destroying collagen. Oxytocin acts as a buffer to the stress-inducing effects of cortisol. When oxytocin goes down, cortisol goes up, and people experience more stress, anxiety, and depression. Conversely, when oxytocin increases, cortisol decreases. 

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