The Truth About Osteoporosis:
Multiple Causes, Multiple Targets
Most of us assume that our bones are like pieces of rocks or hard shells. However, bone is a living tissue, constantly undergoing demolition and renewal as it responds to changing forces in the environment (Martin 2009, Body 2011). Bone is also the body’s primary reservoir of the calcium needed for a wide variety of biological processes (de Baat 2005). Bone is now recognized as an endocrine organ, secreting compounds that function like hormones throughout the body (Kanazawa 2010).
Our bones are made of crystals of calcium salts in a protein matrix. Specific cells, called osteoblasts, produce the matrix and attract calcium compounds to form new bone, while a different set of cells, called osteoclasts, resorbs the bone tissue to allow new shapes and structures to form in response to gravity and the pull of muscles. This process of remodeling helps repair microdamage that occurs as a result of daily activity and prevents the accumulation of old fragile bone (Martin 2009, Mitchner 2009, Body 2011).
At the simplest level, osteoporosis occurs when more bone is resorbed than formed (Banfi 2010, Chang 2009). There are multiple causes for osteoporosis including suboptimal nutrition, age-related hormonal imbalance, and lack of weight-bearing exercise, to name a few (Body 2011).
Perhaps the earliest contributing lifestyle factor is lack of weight-bearing exercise, as many as 20% of young and middle aged women already have an abnormal spinal curvature related to bone loss in their vertebrae, a situation that only get worse as one ages (Dwyer 2006, Cutler 1993). A sedentary lifestyle reduces the constant forces that bone needs to experience in order to continue its normal process of remodeling (Akhter 2010). Studies show that both women and men who engage in regular exercise have much lower risk of osteoporosis and fracture (Ebeling 2004, Englund 2011).
Vital hormones such as estrogen and testosterone promote bone formation and regulate bone resorption, and when those hormone levels drop, osteoporosis can occur. At puberty, bone production increases dramatically, producing the growth spurt of the early teen years. This effect seems to be driven mostly by estrogens, the “female” hormones, in both boys and girls (Gennari 2003, Clarke 2009). Near the end of puberty, androgens, the “male” hormones, increase in both women and men. The androgen surge fuses the bone growth plates, with the result being that the bones can no longer elongate. Young adults generally maintain a steady-state balance in which new bone formation is nearly equal to bone resorption.
Sex hormones also remain at roughly steady levels throughout young adulthood and early middle age (Clarke 2009). After about the age of 35, however, the total amount of bone in the body begins to diminish. In women, the process begins fairly sharply with the onset of menopause, when estrogen levels drop dramatically. In postmenopausal women, bone is lost both from the inner and outer surfaces of bones, as bone resorption by osteoclasts exceeds the already reduced new bone formation by osteoblasts. In men, however, new bone formation on the outer surface of bone keeps pace with resorption on the inner surface for much longer (Seeman 1999). This obvious connection probably accounts for the fact that osteoporosis was thought for so long to be a problem unique to women, and may account for the fact that men begin to suffer fractures from osteoporosis about a decade later than women (Hagino 2003), but similar factors are involved (Ducharme 2009).
The discovery that primary control of bone mineralization in both men and women is mediated by estrogens not only enhances our understanding of how osteoporosis occurs in men, but also has dramatic implications for how we can prevent and treat it (Gennari 2003).
Sex Hormone Binding Globulin (SHBG)
SHBG is a protein produced primarily in the liver, and serves to bind estrogen and testosterone (Nakhla 2009). It has long been known that declining estrogen levels in both sexes are significant contributors to bone mineral loss with aging. Experts now recognize that the steady rise in SHBG with aging is directly correlated with bone loss and osteoporosis in both men and women (Hofle 2004, Lormeau 2004). As a general rule the higher the SHBG level, the less estrogen is available to contribute favorably to bone health.
Evidences indicate that the SHBG molecule itself plays another key role in the body: conveying essential signals to the heart, the brain, the bone and adipose (fat) tissue that ensure their optimal function (Caldwell 2009). There’s even a special SHBG receptor molecule on cell surfaces that functions much like the ubiquitous vitamin D receptor protein, helping cells communicate with one another (Adams 2005, Andreassen 2006). In other words, SHBG itself functions much like a hormone.
New studies are finding a direct role for SHBG and its cell surface receptor in bone loss (Hoppe 2010). The association is so strong that some experts are now suggesting routine measurement of SHBG as a useful new marker for predicting severity of osteoporosis (Hoppe 2010).
Insulin Resistance, Blood Sugar, and Glycation
Bone functions as an endocrine organ secreting compounds that act like hormones (Kanazawa 2010). Healthy production of bone matrix protein increases insulin sensitivity in other tissues (Kanazawa 2010, de Paula 2010). Conversely, people with the metabolic syndrome who are insulin resistant have poorer bone quality and an increased risk of osteoporotic fracture (Hernandez, McClung 2010). Metabolic syndrome also raises SHBG levels, further reducing bioavailable levels of estrogen and testosterone (Akin 2009).
Research suggests that advanced glycation end products, or AGEs, are implicated in bone loss. AGEs are formed when proteins interact with glucose molecules to form damaged structures in the body. One study examined the proteins in osteoporotic bones to determine if there was damage by AGEs. More AGEs present resulted in fewer bone-building osteoblasts (Hein 2006). It is suggested that limiting AGE formation by maintaining a healthy blood sugar level may slow the osteoporotic process (Valcourt 2007).
Oxidation and Inflammation
Oxidation of fatty acids and other molecules produces reactive oxygen species that directly and indirectly impair new bone formation and promote excessive bone resorption (Graham 2009, Maziere 2010). In a similar fashion, chronic inflammation hastens the absorption of existing bone while impeding normal production of new bone (Chang 2009). Fat cells produce a steady efflux of inflammatory cytokines while diminishing cells’ insulin sensitivity; both factors further impede normal bone production (Mundy 2007, Kawai 2009).
For healthy, mineral-rich bone to form, healthy bone matrix protein must be produced (Bugel 2008, Wada 2007). Over the past decade scientists have realized that vitamin K is an essential co-factor for production of the major bone protein, osteocalcin (Bugel 2008, Iwamoto 2006). Vitamin K-dependent enzymes produce changes in osteocalcin that allow it to tightly bind to the calcium compounds that give bone its incredible strength (Bugel 2008, Wada 2007, Rezaieyazdi 2009).
Calcium and Vitamin D
Many other environmental and nutritional factors contribute to the gradual development of osteoporosis. The role of low intake of vitamin D and calcium are well known (Cherniack 2008, Lips 2010). Adequate calcium intake is required to allow healthy bone remodeling and prevent osteoporosis. Vitamin D promotes intestinal absorption of calcium, and also regulates how much calcium enters and leaves bone tissue in response to the body’s other calcium requirements.
While bone is primarily composed of matrix protein and calcium compounds, small amounts of other trace minerals are essential for normal bone function. These include magnesium, which regulates calcium transport; silicon, which reverses loss of calcium in the urine; and boron, which interacts with other minerals and vitamins and also has anti-inflammatory effects (Aydin 2010 Mizoguchi 2005, Kim 2009, Li 2010, Spector 2008, Scorei 2011).
The conventional model of osteoporosis predicts that simple restoration of declining sex hormone levels and provision of modest amounts of calcium and vitamin D should be sufficient to prevent osteoporosis. When those steps fail (which they inevitably do), conventional medicine resorts to suggesting that osteoporosis must be an inevitable consequence of aging.
Life Extension’s® position, however, is much more nuanced and incorporates the truth about the complex, interrelated factors that genuinely contribute to osteoporosis. Life Extension recommends a lifelong commitment to an active lifestyle, and supplementation with targeted vitamins, minerals and nutrients that quench reactive oxygen species (ROS), reduce inflammation, control obesity and insulin resistance, promote healthy bone matrix protein synthesis, and supply sufficient trace minerals to support healthy bone.