Bone Healing & Opioids Essay
Bone fractures are the most important cause of severe acute pain in osteoporosis, which is later often followed by chronic musculoskeletal pain due to dorsal kyphosis, exaggerated lordosis or compression of nerve roots or spinal cord. The functional stress on spinal muscles and ligaments results in the development of chronic back pain and impaired mobility. Injured structures in the lumber spine can also produce referred pain or a true radicular pain.
Drugs against osteoporosis may have some analgesic effects, as has been shown for denosumab or bisphosphonates like pamidronate. Similar results have been obtained with calcitonin, which is no longer available for the treatment of osteoporosis. Selective estrogen receptor modulators like raloxifene and the anabolic drug teriparatide can also reduce osteoporotic pain and augment fracture healing.Bone Healing & Opioids Essay
The vicious circle of osteoporotic pain, immobility, muscle atrophy and enhanced osteoporosis has to be interrupted by an effective multimodal pain management. Beside the treatment of osteoporosis and fractures, analgesic drugs play a major role in restoring physical functioning and mobility. The mainstay in pain management of osteoporotic fractures is the WHO 3-step analgesic ladder with the combined use of non-opioids (NSAIDs, paracetamol) with weak opioids like tramadol for mild to moderate pain, or strong opioids like morphine, hydromorphone, oxycodone, buprenorphine, fentanyl or tapentadol for moderate to severe pain. The combination of nonopioids with oral controlled release (CR) strong opioids or prolonged release (PR) tapentadol provides excellent analgesia even in severe pain from osteoporotic fractures. This is also true for transdermal therapeutic systems containing fentanyl or buprenorphine (skin patches).Bone Healing & Opioids Essay
There are differences in the relative fracture risk of opioids, which is highest with fentanyl and lowest with buprenorphine. Some opioids influence the endocrine system, particularly the sex hormones, and lowered testosterone and estrogen levels finally reduce bone
density. Tapentadol is an exception, which acts simultaneously as a μ-opioid receptor agonist (MOR) and a noradrenalin reuptake inhibitor (NRI). It has minor effects on the endocrine system and sex hormones and should therefore be favored for long-term treatment of osteoporosis pain. The synergism between its two analgesic mechanisms improves analgesia and reduces adverse events.
In conclusion, the standard treatment of acute and chronic pain after osteoporotic fracture is a multimodal analgesic therapy including non-opioids, opioids, mobilization and rehabilitation. Opioids with minor effects on
the endocrine system and bone density, such as buprenorphine or tapentadol, should be preferred for long-term pain management in these patients.
According to the Institute of Medicine, chronic pain affects approximately 100 million American adults—more than the total affected by heart disease, cancer, and diabetes combined.1 The use of opioids for treatment of chronic pain has increased substantially over the past decade—nearly doubling from 11.3% to 19.6% between 2000 and 2010.2 Estimates suggest that millions of patients take opioids daily to control pain.3,4Bone Healing & Opioids Essay
Side effects of opioid treatment are fairly common and can affect the gastrointestinal (constipation, nausea), central nervous, cardiovascular, and genitourinary systems. One side effect that is often overlooked but increasing in frequency is the effect opioids have on the musculoskeletal system. More specifically, opioids are being recognized as a risk factor for bone loss in patients who take them chronically. Bone loss initially is a silent process, making it less likely that physicians will consider it in evaluating patients on opioids. Bone loss over time, however, can cause a significant increase in the risk of osteoporosis and fractures, increasing the cost of care for patients and affecting quality of life.
In this article, we will explore the causes of opioid-associated osteoporosis, screening recommendations, and potential treatment options.Bone Healing & Opioids Essay
What Causes Opioid-associated Osteoporosis?
Patients on long-term opioids appear to be at higher risk of developing osteopenia and osteoporosis. Duarte et al found that 50% of patients receiving intrathecal opioids demonstrated osteopenia (defined as T score between -1.0 and -2.5 SD), with more than 20% diagnosed with osteoporosis (T score </ -2.5 SD).5 Other sources report the incidence of osteoporosis in hypogonadal men to be as high as 50%.6
Gender has shown to have a varying effect on the risk for developing opioid-induced osteopenia/osteoporosis. In one study, men and women both develop premature osteoporosis that was thought to be caused by chronic opioid use.7 Women demonstrated bone densities in the osteoporotic range prior to age 40 at a much higher rate than expected.7 Men in the study frequently had testosterone levels <50 ng/dL (in the male castrate range), which was associated with osteopenia.7 However, in a study of patients in a methadone maintenance program, only men demonstrated lower bone mineral density scores. In the study, by Grey et al, men had a 10% lower bone density as compared to controls, whereas women had bone densities approaching those of the age-matched general population.8 The 10% lower bone mineral density is associated with a 2-fold increase in the relative risk of fractures in this population. Further studies will be needed to determine the exact role gender has on opioid-associated osteoporosis, given the 2 conflicting studies.
The exact mechanism is not fully known, but it appears to be multifactorial. The main contributing factors seem to be the development of endocrinopathy, direct osteoblast inhibition, mental status changes, and associated comorbities.Bone Healing & Opioids Essay
Endocrinopathies
One of the leading causes for the bone density changes seen in patients on opioids seems to be endocrinopathies (Figure 1). Normally the hypothalamus secretes gonadotropin-releasing hormone (GnRH), which acts upon the anterior pituitary, releasing luteinizing hormone (LH) and follicle stimulating hormone (FSH). The anterior pituitary, along with growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), adrenalcorticotrophic hormone (ACTH), LH, and FSH, has an altered response to GnRH.6 These hormones have a direct effect on the production of sex hormones in the ovaries or testes, particularly testosterone.
Bruce Bonanno, MD, a Diplomate of the Board of Certification in Emergency Medicine (BCEM), has been practicing emergency medicine for 33 years. Presently at the CentraState Medical Center in Freehold, N.J., he has served in 23 different emergency rooms, from inner city hospitals to rural ones, across several states. Over the years, the wealth of knowledge and experience he has gained from encounters with patients addicted to opioids qualifies him as a respected voice among physicians committed to finding a solution to the current opioid crisis.
Unfortunately, Dr. Bonanno says, the media has followed the lead of politicians in laying blame for the crisis at the feet of health care providers. While opioids are being prescribed more than ever, and there are indeed doctors who may operate “pill mills,” he says that other salient facts do not get reported. For instance, the rise in opioid prescriptions has coincided with an increase in the average age of the general population. This means that the number of people living with chronic painful conditions has also increased, as well as the number of people who have suffered broken bones from falls, who have had hip and knee replacements, and who are in compassionate palliative and hospice care – all conditions that may warrant prescription pain medications. Furthermore, the number of prescribed medications for all conditions has also risen, not just for pain.Bone Healing & Opioids Essay
Prescribers are doing their part to curtail America’s opioid problem, he says. Recent figures show that the number of opioids prescribed has leveled out or decreased. As for the argument that many people who have died from illegal drugs were first addicted to prescription meds, the truth is that most people who became addicted to prescription meds were never prescribed them in first place. Instead, they obtained prescription drugs from family and friends in an attempt to get high. Part of the problem, he says, is that the medication left over after patients have quit using them frequently remains in medicine cabinets for anyone to use.Bone Healing & Opioids Essay
Dr. Bonanno also points out that the illegal opioid heroin has caused most of the recent deaths from opioid overdose. A decrease in the price of heroin, coupled with an increase in purity, has only exacerbated the problem. Now, with fentanyl, a synthetic opioid, added to the mix, the results have been calamitous.
Another reason to be skeptical about the narrative that faults doctors’ prescriptions for the rise in opioid overdose deaths, according to Dr. Bonanno, is that many of the original statistics were inaccurate. For example, opioid deaths were lumped together regardless of whether they were the result of legal or illegal drugs, or whether opioids were really the cause of death as opposed to just being present in the body at the time. In addition, the quality of training of the authorities reporting on opioid deaths varies considerably. When you consider in particular that distinguishing between prescribed and illegal fentanyl is very difficult, it’s easy to see how many overdose deaths could have been mischaracterized.