The Scariest Skeleton Is the One with Osteoporosis

It’s spooky season, and there’s nothing more spooky than skeletons. Specifically, the skeletons inside our bodies (very spooky), and even more specifically, when those skeletons are too fragile to allow for trick-or-treating. Osteoporosis is a condition where the internal structure of bones deteriorates, making them weaker and more likely to break.^[1] Osteoporosis affects around 5% of men and 27% of women over 65 years of age  in the United States, and rates are increasing.^[2,3] People with osteoporosis have around a 40% lifetime risk of breaking a bone. In the US, osteoporosis is involved in around 2 million broken bones every year - primarily in the wrist, spine, and/or hip.^[2,3,4,5] To understand what happens in osteoporosis, let’s first build a backbone of knowledge about what the skeleton is and how it works normally.

The most important thing to remember about our bones is that they are very much alive. When we see skeletons out and about (y’know, like ya do), they are all white and brittle, but that’s because they’re dead (or, hopefully, fake). Living bones are flexible, active, and useful; bones provide the structure muscles need to move, regulate the distribution of minerals in the blood and body, and actively make blood cells!^[1] Bones aren’t all minerals and calcium (though that does make up around 60% of their weight), but are full of myriad organic proteins and cells.^[1] Most of what’s called the “organic phase” of bone is collagen, a structural protein that keeps everything together, with the rest being made of other proteins and some key cells.^[1] These cells are critical to a major function of bone, remodeling.

Bones aren’t set in stone, they’re made of calcium, minerals, cells, and proteins. Remodeling is the body’s natural process of breaking down these materials in some parts of bones and building them up in others.^[1] Bones that are actively used are reinforced with extra material taken from lesser-used bones.^[1] As an example, tennis players have larger bones in their dominant arm compared to their nondominant arm.^[1] In adults, around 4-10% of bone mass is remodeled yearly, while in infants this number can be as high as 50% for some bones.^[1]

The prefix osteo- is Greek for “bone,” and two of the major cells which remodel bones are called osteoclasts and osteoblasts. Osteoclasts are cells that break down bone; they help keep the bone efficient and lightweight. Osteoblasts deposit material to build bone up. A healthy bone is in perfect balance, with osteoclasts and osteoblasts working in concert to make bones light, efficient, and reinforced where they need to be. The balance between osteoclasts and osteoblasts depends on genes, hormones, signals from sensory cells, and the amount of calcium and nutrients in the blood.^[1] The balance is also age dependent, with bone mass peaking in the late 20s and early 30s and staying pretty similar until around 50 years of age.^[6] In women, menopause marks a turning point where bone density begins to decrease, increasing the risk of osteoporosis.^[1]

The word “osteoporosis” is made of the Greek words osteo- for bone, por- indicating holes or pores, and -osis which means a state or condition. Osteoporosis is a condition where the bones become more porous, or as physician Fuller Albright put it, “too little bone in the bone.”^[7] In osteoporosis, bone-dissolving osteoclasts outperform the bone-building osteoblasts and bones become less dense.^[1] This loss of density means a loss of strength and an increase in the risk of a bone fracture. Risks of broken bones increase with age, low BMI, family history, some medication use (including glucocorticoids), and smoking.^[5]

This all sounds very spooky, so what can be done? The goal of osteoporosis therapy is to reduce fractures, so reducing risk factors is a critical first step. This includes quitting smoking, reducing alcohol, increasing exercise (to induce osteoblast activity), and correcting any vitamin or mineral deficiencies like vitamin D or calcium (talk to a doctor before taking supplements!).^[5] Osteoporosis medications fall into two major categories: those that slow osteoclast activity (bone reabsorption) and those that increase osteoblast activity (bone formation).^[5] Antireabsorptive medications called bisphosphonates have been the standard of care for a long time, can be injected or orally taken, have a record of safety, and can be inexpensive.^[5]  Some people cannot tolerate the side effects, and many people still suffer from osteoporosis-related fractures, however. That’s why new medications aimed at restoring the balance of osteoclasts and osteoblasts continue to be developed through clinical research. Other medications include hormones and hormone-like molecules to increase bone formation, called anabolic drugs and drugs that specifically target postmenopausal women like raloxifene.^[5] Newer classes of medications, like the monoclonal antibody denosumab, target osteoblasts, osteoclasts, or the signaling processes between them with high specificity and may provide a different or lower side effect profile.^[5] With the help of clinical trials, we may be able to keep the skeletons in our bodies strong and scare-free.

Creative Director Benton Lowey-Ball, BS, BFA

References:

[1] Marcus, R., Dempster, D. W., Cauley, J. A., & Feldman, D. (Eds.). (2013). Osteoporosis. Academic Press. 

[2] Reginster, J. Y., & Burlet, N. (2006). Osteoporosis: a still increasing prevalence. Bone, 38(2), 4-9. https://www.sciencedirect.com/science/article/pii/S8756328205005272

[3] Sarafrazi, N., Wambogo, E. A., & Shepherd, J. A. (2021). Osteoporosis or low bone mass in older adults: United States, 2017–2018. NCHS Data Brief, no 405. National Center for Health Statistics. https://www.cdc.gov/nchs/products/databriefs/db405.htm

[4] Burge, R., Dawson‐Hughes, B., Solomon, D. H., Wong, J. B., King, A., & Tosteson, A. (2007). Incidence and economic burden of osteoporosis‐related fractures in the United States, 2005–2025. Journal of bone and mineral research, 22(3), 465-475.

[5] Rachner, T. D., Khosla, S., & Hofbauer, L. C. (2011). Osteoporosis: now and the future. The Lancet, 377(9773), 1276-1287. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62349-5/

[6] Akhiiarova, K., Khusainova, R., Minniakhmetov, I., Mokrysheva, N., & Tyurin, A. (2023). Peak bone mass formation: modern view of the problem. Biomedicines, 11(11), 2982. https://link.springer.com/article/10.1007/s001980070020

[7] Albright, F., & Reifenstein, E. C. (1948). The Parathyriod Glands and Metabolic Bone Disease. https://www.cabidigitallibrary.org/doi/full/10.5555/19512200496