Regular, heavy users of cannabis have a lower bone-mineral density and are more likely to suffer fractures than regular smokers of cigarettes who do not use the drug, the results of a cross-sectional study indicate.
The research, which is published online in the American Journal of Medicine, shows that the bone density of heavy cannabis users was approximately 5% lower than that among control smokers and that they had more than double the fracture risk of controls.
"Our research has shown that heavy users of cannabis have quite a large reduction in bone density compared with nonusers, and there is a real concern that this may put them at increased risk of developing osteoporosis and fractures later in life," said senior author Stuart H Ralston, MD, from the Centre for Genomic and Experimental Medicine, the University of Edinburgh, Scotland, in a press release.
Speaking to Medscape Medical News, he noted that bone-mineral density "is influenced by many, many factors," such as smoking, alcohol, genetics, diseases, and diet. Taking into account as many possibly confounding factors as possible, they found that the association between heavy cannabis use and bone-mineral density was partially mediated by body mass index (BMI).
He explained: "One thing we found was that cannabis users, the heavy users especially, had a low body weight, which was a bit of a surprise, because cannabis classically stimulates appetite, but we think that maybe, longer term, it has an anorectic effect, if you're [smoking] it all the time."
Dr Ralston believes that the findings, when put together with those on the psychological impact of cannabis use, underline that there is still a lot to learn about its effects, particularly given ongoing efforts to have the drug legalized.
"People think: 'Well, what harm can cannabis do?' There's a lot of stuff in the psychiatric literature showing that cannabis, in susceptible people, can predispose to psychosis….This is additional research that shows that, in terms of physical health, if you take a lot of cannabis, it reduces your bone-mineral density."
First Look at Cannabis Effect on Bone in Humans
The researchers note that although they have looked at the effects of cannabis on bone metabolism in cell studies and in rodents, this is the first work to examine the effects of the drug on bones in humans.
They conducted a cross-sectional study of 200 regular cannabis smokers recruited from primary care between 2011 and 2014.
The participants were divided into moderate (n = 56) and heavy (n = 114) cannabis users, based on whether they reported ≤ 5000 lifetime cannabis smoking episodes. In addition, 114 smokers who reported five or fewer cannabis smoking episodes were recruited as controls.
The average heavy cannabis user was found to have taken the drug more than 47,000 times, while moderate users reported that they had taken the drug an average of 1000 times.
Cannabis users were significantly younger than controls, at a mean age of 40.5 years for heavy users vs 49.5 years for controls. Cannabis users were also less likely to be female than smokers, and female cannabis users were significantly less likely to be postmenopausal than controls.
There were no significant differences between cannabis users and controls in terms of alcohol use and, for heavy users, tobacco pack-years, although moderate cannabis users had significantly fewer tobacco pack-years than controls.
There were also no significant differences between the groups in terms of how often they participated in sports. However, heavy cannabis users had a significantly lower mean BMI than controls, at 26.5 kg/m2 vs 29.0 kg/m2 (P = .01).
Heavy Cannabis Use Is Independent Predictor of BMD at Hip, Femur
Using dual-energy X-ray absorptiometry, the researchers found that heavy cannabis users had a significantly lower total hip bone-mineral density than controls, at a mean Z-score of -0.20 vs +0.20 (P < .0005), and a lower spine bone-mineral density, at -0.5 vs 0.0 (P < .0005).
In addition, heavy cannabis user had a significantly increased fracture rate compared with controls, at a ratio of 2.17 (P < .001).
The results also show that serum concentrations of the bone metabolism biomarker C-terminal telopeptide of type 1 collagen were raised in heavy cannabis users compared with controls, at 0.3 pg/mL vs 0.2 pg/mL (P = .045).
Serum levels of N-terminal propeptide of type 1 procollagen were also increased in heavy cannabis users, at 47.1 pg/mL vs 41.2 pg/mL (P = .01).
In contrast, serum 25(OH)D concentrations were reduced in heavy users vs controls, at 25.3 nmol/L vs 36.9 nmol/L (P = .002).
Heavy cannabis use was found on multivariate regression analysis to be an independent predictor of spine, femoral neck, and total hip bone-mineral density, accounting for 5.4% (P = .035), 3.9% (P = .010) and 5.8% (P = .001) of the variance, respectively.
However, BMI explained a part of the variance in bone-mineral density, accounting for 38.7% (P = .002), 32.3% (P = .001), and 55.2% ( P = .001) of the difference at the lumbar spine, femoral neck, and total hip, respectively.
Mediation analysis suggested that the effect on spine bone-mineral density from heavy cannabis use was indirect and mediated through low BMI, although heavy cannabis use had a direct, negative effect on femoral neck and, in particular, total hip bone-mineral density.
Implications for Medical Marijuana Users?
The current findings build on previous work by Dr Ralston and colleagues on the biochemical impact of cannabis on bone metabolism.
He said: "We have worked in this area for more than 10 years, and we've done a lot [of work] in mice and in cell cultures showing that cannabis, or its components, stimulate osteoclasts.
"But this is the first study in humans, so we think it's an important study and hopefully will raise interest in doing further research."
To those ends, Dr Ralston would be interested in examining the effect of cannabis over time in longitudinal studies.
"A question that I've been asked and one that I'm wondering about is that among people.…with multiple sclerosis or with pain, there's anecdotally [a lot] of people using cannabis to try to help control that. It would be quite important to find out, by looking at those groups of patents, if there is evidence of harm there, because…people with multiple sclerosis have low bone-density anyway because they're not mobilizing properly. If the cannabis were to make that worse and predispose them to a fracture, then obviously that would not be good."
The study was supported by a program grant from Arthritis Research UK. Dr Ralston is the inventor on a patent concerning the use of cannabinoid-receptor ligands as treatments for osteoporosis and other bone diseases. The coauthors have no relevant financial relationships.
Am J Med. Published online September 1,2016. Abstract
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