Testosterone and Bone Health

The integrity of the skeletal system is maintained by a complex process known as remodeling. The process of bone remodeling is governed by three major types of bone cells: bone-forming osteoblasts, bone-resorbing osteoclasts, and mediator osteocytes. [342] These bone cells are very sensitive to signaling conveyed through hormones, particularly testosterone. Dysfunction of these cells is the primary cause of dysregulation of the remodeling process, which ultimately lead to bone loss and bone disorders.
As men age, their testosterone concentrations in the blood start to decline, as do their bone densities. Because testosterone plays a crucial role in the signaling of the bone cells, the age-related decline in this hormone may ultimately lead to dysregulation of the bone remodeling process. This in turn causes osteoporosis, a bone disease characterized by weak and fragile bones. Researchers found that there is a high incidence of early bone loss and low bone density (osteopenia) in men with low levels of testosterone which increases their risk of osteoporosis. [343] And the longer the duration of testosterone deficiency, the greater the risk.
Sex steroids in both sexes play a pivotal role in the maintenance of bone quality. Numerous high quality studies even found that low testosterone levels are associated with a higher risk of osteoporosis and other bone disorders. [345-349] It seems reasonable to anticipate that low levels of testosterone in aging men and women would correlate to a loss in bone mineral density (BMD) and an increase in the risk of fractures, and that testosterone replacement therapy may have beneficial effects on bone quality.
Because bone density is also low in hypogonadal men, testosterone replacement therapy would help restore bone density to healthy levels. In one study investigating the effect of testosterone treatment on bone mineral density in men over 65 years of age, Snyder et al. reported that testosterone patch did increase bone mineral density of the lumbar spine as well as blood testosterone concentrations after 36 months of treatment. [350]
In a similar study, Amory et al. investigated the effects of testosterone therapy and finasteride, a 5 alpha-reductase inhibitor (prevents conversion of testosterone), among 70 men aged 65 years and older with low testosterone levels for over 36 months. [351] The study showed that the combination of testosterone therapy and finasteride increased vertebral and hip bone mineral density (BMD), which is indicative of improved bone quality.
Growing evidence also suggest that testosterone replacement can be beneficial in improving bone mineral density and lowering fracture risk in men with osteoporosis and hypogonadism. In fact, the Endocrine Society of North America recommends testosterone replacement therapy in symptomatic hypogonadal males to improve their symptoms and enhance bone mineral density. [352] This recommendation appeared in their clinical guidelines in 2010. Moreover, the 2012 Endocrine Society Osteoporosis in Men guideline also recommends testosterone replacement therapy in men with symptomatic low testosterone who are at high risk of fracture. [353]
There also have been a number of clinical trials assessing the effect in men of testosterone replacement therapy on bone quality and strength, regardless of underlying testosterone levels, which generally resulted in a significant improvement in bone mineral density. In one study, Hoppéa et al. conducted a review of 14 clinical trials assessing the beneficial effects of testosterone replacement therapy in men, all of which looked at bone mineral density at the lumbar spine and femoral head, without fracture risk outcomes. [354] With regards to the bone mineral density of the lumbar spine, 5 out of the 14 clinical trials showed significant increases. Because of these positive results, the authors concluded that there was sufficient evidence to support the benefit of testosterone replacement therapy in lumbar spine bone mineral density.
There also have been additional studies in men that have provided further strong evidence for the therapeutic benefit of testosterone replacement therapy on lumbar spine and femoral bone mineral density. For instance, a study by Permpongkosol et al. evaluated the effects of testosterone treatment in 120 late-onset hypogonadal males (mean age is 65.6 years old). [355] The study participants received intramuscular testosterone injections for 5 to 8 years, the longest study to date. Surprisingly, researchers observed a significant increase in bone mineral density of the lumbar spine and femoral neck after 48 months of treatment.
Other studies have also shown that aside from injections, testosterone treatment may also be effective if taken orally or applied to the skin. In a study by Wang et al., oral low dose testosterone treatment among 186 hypogonadal males aged 60 and above with osteoporosis at baseline, resulted in significant increases in the bone mineral density of the lumbar spine and femoral neck after 6 to 12 months. [356]
A similar study by Bouloux et al. involving 322 hypogonadal males aged 50 and above found that intermediate and high doses of oral testosterone resulted in significant increases in bone mineral density of the lumbar spine, total hip, trochanter (upper part of the thigh bone), and intertrochanteric sites. [357]
Also, a study by Rodriguez-Tolra et al. found that application of topical testosterone gel among 50 hypogonadal males aged 50 and above resulted in significant increases in the bone mineral density of the lumbar spine at both 12 and 24 months, and in the total hip and trochanter at 24 months only. [358]
Numerous clinical trials have also shown that testosterone replacement therapy may significantly increase bone mineral density in different body parts and reduce the risk of fractures as well as other bone disorders. [359-374]

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