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Article: Harald Dobnig, Jutta Claudia Piswanger-Sölkner, Barbara Obermayer-Pietsch, Andreas Tiran, Andrea Strele, Elisabeth Maier, Peter Maritschnegg, Gunter Riedmüller, Carolin Brueck, and Astrid Fahrleitner-Pammer Hip and Non-Vertebral Fracture Prediction in Nursing Home Patients: Role of Bone Ultrasound and Bone Marker Measurements J Clin Endocrinol Metab 2007; 0: jc.2006-2079v1 [Abstract]

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Opiates and fracture

Jose L Perez-Castrillon, Antonio Dueñas-Laita   (22 May 2007)

Opiates and fracture 22 May 2007
Jose L Perez-Castrillon, Internal Medicine University Hospital Rio Hortega, Antonio Dueñas-Laita Send letter to journal: Re: Opiates and fracture castrv{at}terra.es Jose L Perez-Castrillon, et al.	We read the paper of Dobnig et al. (1) which shows the role of calcaneal stiffness measurements in predicting hip fractures and non-vertebral fractures in nursing home residents. An interesting aspect of their data is the positive relationship between opiates and hip and non-vertebral fracture, which the authors attribute to a decrease of bone mass mediated by increased bone turnover and less mobility. Similar data were observed by Vestergaard et al. (2), who examined the effect of opiates in a population-based study and found a trend towards an increase in fracture risk. These drugs may increase the risk of falls by altering postural balance. We propose that another possible explanation is a direct effect of opiates to bone cells. The activity of exogenous opiates is mediated through specific cell surface of receptors. Rosen et al. (3) have demonstrated that PENK-derived peptides inhibited the activity of alkaline phosphatase and the presence of specific mRNA of κ receptors in rat osteoblasts. Perez-Castrillon et al. (4) have shown that the human osteoblast-like cells MG-63 present immunohistochemical reactivity of µ, δ, and κ receptors and express the three types of opioid receptor genes. Moreover, an opioid receptor blocker, naloxone, administered to chick embryos, increases the pericondral bone in the tubular bone diaphyses and increase mitotic activity in the zone of proliferating young cartilage of the epyphyseal plate (5). In vitro, the morphine induced inhibition of osteocalcin secretion (4). It is possible that opiates inhibit the activity of osteoblast. However, in vivo, Dobnig et al. (1) found a 2-4% increase of osteocalcin levels; but these patients had a high prevalence of vitamin D deficiency and increased PTH, which might explain the higher osteocalcin. Thus, opiates could inhibit the activity of osteoblasts with a weakening of bone structure and an increase fracture risk. References 1. Dobnig H, Piswanger-Sölkner JC, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Riedmüller G, Brueck C, Fahrleitner- Pammer A. 2007. Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone markers measurements. J Clin Endocrinol Metab 92:1678-1686 2. Vestergaard P, Rejnmark L, Mosekilde L. 2006. Fracture risk associated with the use of morphine and opiates. J Intern Med 260:76-87 3. Rosen H, Krichevskya A, Polakiewicz RD, Benzakine S, Barshavit Z. 1995. Developmental regulation of proenkephalin gene expression in osteoblast. Mol Endocrinol 9:1621-1631 4. Perez-Castrillon JL, Olmos JM, Gomez JJ, Barrallo A, Riancho JA, Perera L, Valero C, Amado JA, Gonzalez-Macias J. 2000. Expression of opioid receptors in osteoblast-like cells MG-63, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells. Neuroendocrinology 72:187-194 5. Liskov AV, Solnyshkova TG, Frolov BA, Pavlovichev SA. 2005. Effect of naloxone hydrochloride on osteogenesis in chick embryos. Bull Exp Biol Med 139:331-333