Case study report of PEARL female trial participant with osteopenia showing unexpected beneficial increase in bone mineral density (BMD)

Cureus

2025 Jan 14;17(1):e77435. doi: [10.7759/cureus.77435] (Unexpected Increase in Bone Mineral Density With Rapamycin and Low-Dose Naltrexone: A Case Report of a 52-Year-Old Woman With Osteopenia | Cureus)

Unexpected Increase in Bone Mineral Density With Rapamycin and Low-Dose Naltrexone: A Case Report of a 52-Year-Old Woman With Osteopenia

Editors: Alexander Muacevic, John R Adler

PMCID: PMC11825221 PMID: 39958011

Abstract

Osteopenia and osteoporosis are prevalent bone disorders characterized by reduced bone mineral density (BMD), leading to an increased risk of fractures. This case report presents a 52-year-old Caucasian female patient with osteopenia who experienced an unexpected 15.9% increase in lumbar spine BMD within two years after enrolling in a clinical trial involving low-dose rapamycin and subsequently starting low-dose naltrexone. This case potentially opens novel treatment strategies for bone density improvement in aging populations.

7 Likes

Someone shared this yesterday in another thread and I commented that I started LDN in Jan and had a dexa in the fall, so it will be exciting for me to recheck and see what happens.

I started 6mg of weekly rapa 5/24
I’m also on the same 4.5 of LDN.
Hopefully this means I’ll be another great test case.

I had already been taking d/k, but I added calcium in the fall.

I have been meaning to ask about natto/nattokinase to see if I should consider those. The person in this study was taking it, so perhaps I should

6 Likes

Can someone explain what the possible mechanism of action would be for Naltrexone which is used to curb opiate and alcohol cravings in addicts to aid in bone density?

1 Like

From MS Copilot:
Naltrexone is primarily known as an opioid antagonist, which means it blocks the effects of opioids by binding to opioid receptors in the brain.

While its primary use is in treating opioid and alcohol dependence, there is some emerging research suggesting that it might have potential benefits for bone density.

One possible mechanism is through its action on the opioid receptors. Opioid receptors are not only present in the brain but also in other tissues, including bone. By blocking these receptors, Naltrexone might influence the activity of osteoclasts and osteoblasts, which are cells responsible for bone resorption and formation, respectively.

Additionally, Naltrexone has been shown to have anti-inflammatory properties. Chronic inflammation can negatively impact bone health, so reducing inflammation might help improve bone density

4 Likes

Fascinating! Thank you.

IMO I am not too “impressed” by this and I wouldn’t make any decision based on a single patient.

A single patient can easily be an outlier, and there are many other factors which could have played a role. You can put the same person through a DEXA on a Monday, Tuesday and Wednesday and get different results. The error is 5-10%. (https://onlinelibrary.wiley.com/doi/full/10.1359/jbmr.071119)

So this lady maybe has -5% measurement error before Rapamycin, +5% after Rapamycin, and maybe a real change of 5%, thus stacking up a purported change of 15%. If you recruit a few hundred patients, as they did in this study, you’re going to get a few weird ones.

For example, strength training makes people stronger. But there are strength training papers where some individual people get weaker after 12 weeks of strength training. That’s why we recruit lots of people, look at averages and use statistical tests. There are always outliers, and picking one example really has almost no value IMO. Nobody should be misled into thinking “maybe I can gain 15% too”

2 Likes