It seems that every week or two, there’s a new-found association between obstructive sleep apnea (OSA) and various medical conditions. Besides the typical medical conditions associated with OSA such as high blood pressure, diabetes, heart disease, heart attack, stroke, and even cancer, there have been a handful of studies looking at the link between OSA and osteoporosis.

1. Low levels of oxygen (hypoxia) from apneas can increase osteoclast activity which increases bone reabsorption. Hypoxia has been shown to release a family of messengers (hypoxia inducible factor, or HIF), which help cells to adapt and survive during low levels of oxygen. One of these messengers (HIF-1α) stimulates osteoclast activity. HIF-1α also promotes release of vascular endothelial growth factor (VEGF), which stimulates stem cells to increase bone osteoclast (breaking down) and osteoblast (building up) activity. VEGF  and HIF-1α have also been suggested as one possible pathway that explains how OSA can increase your risk of cancer. Oxidate stress that results from hypoxia is also associated with bone resorption and low bone mass.

3. Bone turnover appears to be influenced by circadian factors and sleep stages. Leptin is an appetite hormone that signals that you have eaten enough food. People with obstructive sleep apnea are found to have higher levels of leptin, and lower on CPAP. Leptin blocks serotonin production in the brain, leading to increased sympathetic tone, on top of an already increased sympathetic state in people with OSA. High levels of leptin and sympathetic tone has been found in patients with lower bone density.

Melatonin and its relation to bone metabolism has been studied extensively. Melatonin receptors have been found on human osteoblasts. In mice, melatonin was found to lower osteoclast function. Since melatonin diminishes with age, this may contribute to higher rates of osteoporosis in the elderly. They speculate that the anti-estrogenic effects of melatonin may play an effect on hormone-dependent cancers (breast, prostate, endometrial).

4. OSA patients have lower levels of Vitamin D and bone mineral density, and higher rates of hip fractures.

5. OSA inhibits certain hormones, especially, thyroid stimulating hormone (TSH), testosterone, leutenizing hormone (LH), and growth hormone (GH). In particular, growth hormone is secreted mainly during slow-wave deep sleep.

6. OSA or poor sleep quality/duration has been linked with mild cognitive impairment (MCI), depression, frailty, falls, and medications that predispose to falling. Certain medications that lower sympathetic tone can also lower melatonin production, since its pathway goes through the superior cervical ganglion. Nasal congestion often results from blood pressure medications, which can aggravate sleep-related breathing problems.

7. Although not in the paper, this is an important point: People who take long-term acid reducing medications (proton pump inhibitors, or PPI) can raise your risk of fractures by 35%. One possible mechanism proposed was that lower acid levels blocked calcium absorption. Magnesium can be lower as well.

Here’s a link to a diagram from the above mentioned paper that summarizes all the above.