The Roots of Osteoporosis
For centuries doctors assumed frail bones and stooped postures were just irreversible aspects of aging. In the 18th century, however, investigators began to uncover hints in experiments with animals that bones undergo continual remodeling throughout life.
Eventually scientists identified the key members of the bone construction crew: three types of specialized cells. Osteoclasts excavate small pits in old or cracked bone, whereas osteoblasts extrude into those pits a blend of soft collagen and other proteins, which they subsequently harden with calcium phosphate and other minerals. A third group of cells, the osteocytes, helps to coordinate skeletal repair via chemical signals to the demolition and construction crews. By overhauling about a million scattered, tiny patches of bone at a time, the adult human body renews its entire skeleton approximately every 10 years.
A remodeled chassis might seem like an automatic upgrade, but cross-sectional views of hips and vertebrae reveal that new bone is not as well crafted as the original. The honeycombed interior of freshly laid trabecular (from the Latin for “small beam”) bone surrounding the marrow has fewer cross-struts to lend it strength and elasticity. Even though the hard outer shell, or cortical bone, grows thicker in some spots over time, autopsies show that these thickened sections are often riddled with holes.
The consequences of this lopsided bone repair—more destruction than construction of the adult skeleton over time—hit women harder and earlier in life than men. In the late 1930s endocrinologist Fuller Albright finally began to puzzle out why. Based partly on the bone-building benefits of estrogen in animal experiments, Albright surmised that the back and hip pain and collapsed vertebrae of his osteoporotic female patients might be related to the sudden drop of estrogen in menopause. He gave some of his patients estrogen, and, sure enough, many reported pain relief. Blood and urine tests for calcium and other bone metabolites confirmed that as long as they were taking the estrogen, they lost less bone.
Albright's findings began to reframe osteoporosis as a treatable progressive disorder. His work launched a new wave of research into bone biology that continues today and has stimulated a lucrative market for drugs that either spur the creation of new bone or—in most cases—slow the loss of old bone. Hip fractures were the main concern because they are so deadly, but many other types of fractures significantly reduce quality of life. As scientists began testing the new drugs, they needed a machine that could detect subtler changes in bone than conventional x-rays. Eventually the DXA scan emerged as the clinical standard for measuring bone density: it compares how hard bone and soft tissue differentially absorb low-energy beams directed at the same spot in the skeleton. As DXA scanners became less expensive in the 1990s, the market for bone drugs soared.