RNase L and Chronic Fatigue Syndrome (ME/CFS): Are Patients at Risk of Weak Bones?

Nijs, J., De Meirleir, K., Englebienne, P. and N. McGregor. 2003. Chronic Fatigue Syndrome: A Risk Factor for Osteopenia? Medical Hypotheses 60 (1), 65-68.

This short paper raises the question whether CFS patients are at risk for weak bones. The authors list three different mechanisms that could operate to reduce bone density in people with CFS. No studies have yet examined whether this occurs in CFS patients.

(1) RNase L: The first hypothesis concerns (not surprisingly) RNase L. The authors suggest that the ankyrin fragments released during RNase L fragmentation could, by interfering with the SUR 1 ABC transporters, cause losses of intracellular potassium. Large scale potassium leakage from the cells could result in increased levels of plasma potassium, a condition that prompts the adrenal cortex – in an attempt to lower plasma potassium levels – to secrete aldosterone, a hormone that enhances tubular secretion. The potassium efflux from the cells is mirrored by a influx of calcium into the cells. This is where the trouble really begins.

Because the bones are the largest reservoir of calcium in the body calcium is scavenged from them if the need arises. The authors speculate that osteoblasts (bone cells) in CFS patients may be breaking down bone calcium to maintain ion flows in cells.

An additional ramification of this process concerns the amplification of two calcium activated intracellular proteases, calpain and caspase-12. Since calpain is able to fragment RNase L and caspase plays a role in apoptosis, increased intracellular calcium flows could lead to increased rates of RNase L fragmentation and apoptosis.



(2). Mycoplasmas: Mycoplasmas are bacteria that are commonly found in CFS patients. The most commonly found Mycoplasma, M. fermentans, produces a ‘macrophage activating lipopeptide’ (MALP-2) that induces macrophages to release pro-inflammatory cytokines (nitric oxide, interleukins 1 and 6, tumor necrosis factor alpha (TNF a)) that stimulate the formation of inflammatory mediators called prostaglandins. Each of these cytokines stimulates calcium loss from the bone (bone resorption). Increased levels of the prostaglandin precursor DHGLA and arachidonic acids (an inflammatory mediator) in CFS patients may facilitate this process.

(3) Low IGF-1 levels: Subsets of CFS patients also appear to exhibit low levels of the growth hormone mediator IGF-1 which plays an important role in bone metabolism. Low levels of IGF-1 can result in decreased osteoblast proliferation and shift the balance towards bone breakdown.

*note – some health food stores in the U.S. provide cheap ($20) bone scans.

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