The degree to which different patients respond to any treatment for osteoporosis seems to be related to age.  The degree of loss of bone mineral density (BMD) on a DEXA scan expressed as a T score which is the standard deviations below that in a healthy 30-35 year old.  A T score of -1.0 to -2.5 represents osteopenia and those lower than -2.5 represent osteoporosis.

Generally, a 60 year old with a T score of -2.9 will respond better than a 75 year old with the same T score.  This variance is related to 2 factors, mesenchymal stem cell (MSC) senescence and sarcopenia.  To define those, MSC senescence refers to these cells reaching their reproductive limit.  These stems cells have to produce the new bone producing cells, osteoblasts, each bone remodeling cycle.

As I have discussed in previous blogs, bone develops wear related microcracks.  Those worn areas need to be continually rebuilt.  This is done by remodeling where osteoclasts remove bone from the worn area and then osteoblasts fill new bone back in.  Each year, 10% of the bone is replaced with the entire skeleton being rebuilt each decade.  After the age of 35-40 years, osteoclasts begin to remove more bones with each remodeling cycle, and the osteoblasts build back a little less resulting in a gradual decline in BMD with progressive age.

This loss in BMD accelerates after menopause and further accelerates after the age of 70 years.  The first acceleration after menopause is caused by the decline in estrogen.  The second acceleration after age 70 relates to senescence in the MSCs so they begin to produce fewer osteoblasts, each remodeling cycle worsening the imbalance between how much bone is removed and how much is put back.

All cells including MSCs have a reproductive limit of about 50 cycles.  Once they become senescent, they should die off by programmed cell death called apoptosis.  Unfortunately, some of the senescent cells get stuck in that process and do not die off.  This is problematic as senescent cells develop a SASP or “senescence associated secretory phenotype”,

producing copious amounts of inflammatory cytokines. This inflammation begins to injure adjacent healthy MSCs interfering with their ability to differentiate into new osteoblasts.

The inflammation caused by this inflammatory cytokine production increases the activity of osteoclasts causing them to accelerate bone loss.  At the same time fewer osteoblasts are produced decreasing the bone repair.

As this cell senescence is now understood to be an important aspect of almost all diseases associated with aging, intense efforts are now underway on how this may be treated.  The answer, senolytic therapy.  Different drugs and phytonutrients called flavonoids have been discovered to re-start the cell death pathway in senescent cells reducing the generated inflammation and injury to their adjacent healthy cells.

Perhaps the most effective senolytics is the combination of the flavonoids fisetin and quercetin.  Using this combination causes elimination of the senescent MSCs preventing injury to their healthy cells restoring osteoblastic numbers and bone repair.

As mentioned at the beginning of this, sarcopenia is the other factor that makes osteoporosis treatment response more muted after the age of 70.  Sarcopenia is the medical term for muscle loss.  While muscle loss tends to gradually occur after about the age of 40, it tends to accelerate with older age.  Age related muscle loss can be slowed with a heathy diet with adequate protein and the most important factor, exercise.

While people generally exercise less with age, the need to regularly participate in it increases with age!  As would be expected, a lot of research has been done on the impact of exercise on BMD.  In a study of 60-75 year old women, 3 types of exercise were compared. (1)  The first group (CE) did a program involving different exercises like toe raises and squats.  A second group did these exercises plus used whole body vibration (WBV).  The third group did the same exercise program but wore a weight vest.

All groups had improved lean mass in 8 weeks and improved functional ability. While the CE and WBV groups maintained BMD at follow-up, it actually increased in the weigh vest group.  This likely relates to the increased loading down through the spine and hips with the vest. Loading through those areas stimulates bone generation.  Exercise causes muscle to release a signaling factor irisin which stimulates MSCs to produce osteoblasts.

Unquestionably, treating osteoporosis becomes more challenging after the age of 70 years.  To meet that challenge we have to look at more factors as part of an effective treatment program.

1. Tantanasest et al. Comparative Effects of Weighted Vest and Whole-Body Vibration Training on Bone and Muscle Health in Osteopenia. Life (Basel). 2026 Feb 1;16(2):229.