Male Osteoporosis: An Under-Recognized Threat

by Nieske Zabriskie, ND, PA-C

Osteoporosis is a disease characterized by reduced bone mineral density (BMD), breakdown of the structural architecture of the bone and increased risk of fractures. Osteoporosis is typically thought to affect older women and is often overlooked in men. However, there is substantial data that indicates that osteoporosis in men is becoming an increasingly important public health problem.

This condition is a major health threat affecting 55 percent of Americans 50 years of age and older. Currently, in the United States, there are 10 million Americans with osteoporosis and an additional 34 million with low bone mass, known as osteopenia, who are at increased risk of developing osteoporosis. Of the 10 million Americans with osteoporosis, 20 percent (approximately two million) are men.¹

Osteoporosis is responsible for over 1.5 million fractures annually. Research indicates that 25 percent of men age 50 and older will have an osteoporosis-related fracture in their lifetime. Furthermore, 80,000 men have a hip fracture each year, and one-third of these men die within a year of the fracture.² Although the rate of osteoporosis-related hip fractures is two to three times higher in women than in men, the risk of mortality within one year of the fracture is nearly double for men compared to women.¹

Testosterone as a Bone Builder

One of the primary factors attributed to osteoporosis risk in men is decreasing androgens. Andropause is a condition in which androgen hormones such as testosterone and dehydroepiandrosterone (DHEA) decline with age. The primary androgen hormone, testosterone, peaks around age 20 and then slowly decreases with increasing age at a rate of approximately 1.6 percent per year.

As men age, there is an increase in binding of testosterone to a carrier protein known as sex hormone binding globulin (SHBG), which makes it unavailable for physiological activity in the tissues.⁴ Estrogen levels in men increase with age due to the conversion of the androgens testosterone and androstenedione to estrogen by an enzyme called aromatase. Aromatase is found in many types of tissues including fat cells, making total body fat a factor in the decline of androgens and increase in estrogens.⁵

Further confirming the link between low testosterone and bone loss in men is that men treated for prostate cancer with androgen deprivation therapy (ADT) have a significant increase in the risk of osteoporosis. One study found that in men with prostate cancer treated with ADT, 41 percent had osteoporosis, 39 percent had osteopenia and only 20 percent had normal BMD. Furthermore, of the subjects with normal BMD, there was a significant decrease in BMD of 1.8 percent after one year, 6.5 percent at three years and 12.7 percent at six years. In the group with osteopenia, 60 percent developed osteoporosis within two years of ADT treatment.⁶ Another study found that in men taking ADT for prostate cancer, 33 percent had osteoporosis of spine, hip or forearm according to dual energy x-ray absorptiometry (DXA) evaluation.⁷

Bone-Destroying Medications

Certain pharmaceuticals also play a role in the development of osteoporosis in men. A large study evaluated 62,865 men 50 years or older for prescription usage and fracture risk. The researchers showed that numerous drugs including sedatives, anti-epileptics, anti-psychotics, anti-anxiety, selective serotonin re-uptake inhibitors (SSRI), opioids and other analgesics, loop diuretics, glucorticoids, dopaminergic agents and iron compounds were associated with increased risk of fractures.⁸

Recent research indicates that long-term use of proton-pump inhibitors (PPIs) used to treat heartburn (gastroesophageal reflux disease), inflammation of the stomach (gastritis) and gastric ulcers weakens bones. This is significant as PPIs are the third highest-selling class of drugs in the U.S. In fact, Nexium®, one of the newer PPIs, has the second highest retail sales among all drugs, totaling $4.8 billion in 2008. Furthermore, the number of prescriptions written in the U.S. for PPIs in 2008 was over 113 million.⁹

A large study published in JAMA in December 2006 examined the relationship between PPI use and the risk of hip fractures in individuals over the age of 50. This study found that there was a significant increase in the risk of hip fractures in subjects taking high-dose PPIs for more than one year, and this risk increased as the duration of PPI use increased. More specifically, subjects who took these PPIs for more than one year had a 44 percent increased risk of hip fractures, and taking high-dose PPIs for long periods increased the risk of hip fractures by 245 percent.¹⁰

The study authors suggest that this finding may be due to poor calcium absorption due to the inhibition of stomach acid, as stomach acid is required for optimal intestinal calcium absorption. A similar study published in August 2008 showed that subjects taking PPIs for over five years had an increased risk of hip fracture, and taking PPIs for seven years or more nearly doubled the risk of a osteoporosis-related fracture compared to subjects not taking the drug.¹¹

Another widely prescribed class of pharmaceuticals, the selective serotonin re-uptake inhibitors (SSRIs) used to treat depression, is associated with increased risk of osteoporosis. One study published in June 2007 evaluated the impact of SSRI use and BMD in men 65 years and older. The study found that the men taking SSRIs had BMD 3.9 percent lower at the hip and 5.9 percent lower at the lumbar spine compared to men not taking the drug.¹² Another study published in August 2008 analyzed the risk of falls and fractures in subjects 55 years and older taking antidepressants. The results showed that the risk of non-vertebral fracture increased by more than two-fold for current users of SSRIs compared with nonusers of antidepressants, and the risk continued to increase with prolonged use.¹³

Optimizing Bone Health

Many nutrients and botanicals support bone health. Substantial data supports nutrient intake such as calcium, phosphorus, vitamin D and vitamin K for optimizing the structural integrity of bone. It is well established that calcium supplementation improves BMD. Adding vitamin D3 improves the absorption of the calcium from the intestines and may improve bone quality and strength as well as neuromuscular function, thus reducing the number of falls and decreasing fracture risk.¹⁴

A meta-analysis published in 2009 analyzed 29 randomized studies and found that supplementation with calcium and vitamin D3 reduces risk of bone fractures by 24 percent and significantly reduces loss of bone mass.¹⁵ In addition, research supports vitamin K use to improve bone health. Studies indicate that low levels of vitamin K are associated with low BMD and increased fractures, and supplementation with vitamin K improves the bone turnover profile by reducing bone resorption.¹⁶ Research also indicates that intake of ipriflavone, a synthetic soy isoflavone, and the mineral strontium improve bone integrity by improving bone formation and reducing bone resorption.^17-18

Several botanicals also support bone health by supporting androgen levels. Nettle (Urtica dioica), Eurycoma longifolia jack, beta sitosterol, myricetin (from Myrica cerifera) and luteolin (from Perilla frutescens) support healthy androgen levels. The flavonoid myricetin and the plant sterol beta-sitosterol inhibit an enzyme known as 5 alpha-reductase, which converts testosterone to a metabolite known as 5 hydroxytestosterone.^19-20 Urtica dioica binds to SHGB, allowing more testosterone to be unbound and therefore biologically active.²¹ Also, androgen levels can be maintained with the Perilla frutescens constituent luteolin, which inhibits the aromatase enzyme that converts testosterone to estrogen.²² In addition, the botanical Eurycoma longifolia jack helps elicit androgenic activity, such as improving libido and sexual activity in animals.^23-24

Conclusion

Because men are living longer, they are now at increased risk of developing osteoporosis, which had previously been considered in the medical community as a disease that affects women. Androgen reduction with age, as well as numerous pharmaceuticals, can increase the risk of men developing osteoporosis. Numerous studies support the use of nutraceuticals in maintaining bone health and optimizing testosterone levels.

References

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