Pain Management in Osteoporosis

Abstract

The most prevalent metabolic bone disease, osteoporosis, is characterized by a decrease in bone mineral density and alterations to the bone's microstructure, both of which can result in fragility fractures. It affects a significant section of the population. Acute or chronic pain from these fractures is typical in elderly adults with other coexisting conditions. Since the antiresorptive medication only partially reduces pain, other analgesics are required for effective pain management. NSAIDs or selective COX-2 inhibitors can reduce acute pain, but persistent neuropathic pain is difficult to manage with these drugs. Opioids have their adverse effects and safety concerns, although they can be used to address acute or chronic pain. Hence, a multifaceted approach is to be implemented, including pharmacological and nonpharmacological therapy and surgical treatment in a selected number of cases. This chapter briefly describes the etiology of pain, its mechanism, and pain management in osteoporotic patients.

Background

Osteoporosis is the metabolic bone disease that is most common in the globe and can cause fragility fractures [1]. Osteoporosis is increasing in prevalence due to an older population, and higher life spans; it is now estimated that over 200 million people globally have the condition. According to current data from the World Osteoporosis Foundation [2], one in three women and one in five men over 50 may experience an osteoporosis-related fracture throughout their lifetime.

Fragility fractures involve vertebrae, neck femur, and distal radius and have a high socioeconomic impact. Osteoporotic patients present with chronic musculoskeletal pain leading to disability and impairment in quality of life, which have an adverse financial burden [1, 3]. Fracture vertebra is the most common finding in osteoporotic patients; around 12% of the women in the postmenopausal age group encounter at least one vertebral fracture leading to deformity due to osteoporosis [4]. The skeleton of the aged undergoes several adaptive structural changes, such as bone mass loss, which is frequently accompanied by a decrease in the size and quantity of muscle fibers and results in age-related immobility [5]. Muscle weakness causes axial kyphosis and a continuous loss of bone mass, even in the absence of vertebral fractures [6]. Fragility may lead to multiple vertebral fractures, resulting in progressive stature loss and continuous contraction of paravertebral muscles to maintain body posture. This vicious cycle continued, resulting in muscle fatigue and persistent pain even if the fractures healed [7].

The most commonly reported symptom in osteoporotic patients is lower back pain due to fragility fracture, skeletal deformity, postural imbalance, and muscle fatigue [8, 9]. Hence, the evaluation and management of chronic pain in osteoporotic patients need a holistic approach that takes into account the multiple comorbidities, functional status, daily activity level, and cognitive status of this special group of patients. Pain management should include physical rehabilitation therapy, pharmacological intervention, and surgical treatment if needed [10]. This chapter discusses pain management in osteoporosis, considering recent scientific evidence on pharmacological and nonpharmacological therapies and surgical treatment.

Mechanism of Osteoporotic Pain

The neural system's function in maintaining bone homeostasis is poorly understood, but evidence suggests it is crucial for bone metabolism [11, 12]. The peripheral nerve system (PNS) supplies the skeletal system in great detail. In contrast to a-beta or unmyelinated peptide-poor C-fibres, bone tissues preferentially express a-delta tropomyosin receptor kinase A (TrkA +) and peptide-rich calcitonin gene-related peptide (CGRP)-positive fibers [13, 14]. Since there are almost always the same amount of these neurons in the skeletal system throughout life, there is an increase in innervation as bone mass declines with aging [13].

Numerous local and systemic variables control a crucial balance between osteoblastic and osteoclastic activity in healthy bone; however, this balance falls out of whack in osteoporosis, and osteoclastic activity predominates [15–17]. During increased osteoclastic activity, the vacuolar H + -ATPase secretes protons, producing an acidic microenvironment that breaks down bone minerals. According to studies, this micro acid environment activates the peripheral sensory nerve system's widely dispersed TRPV1 channels [9, 18]. The TRPV1 channels activate the nociceptors in bone and induce pain, leading to neural sensitization; additionally, TRPV1 activation also induces peripheral neuropeptides that promote bone mineral depletion [19–21]. It has been suggested that the PNS is responsible for pain generation and modifying bone homeostasis, predominantly in the catabolic phase of bone metabolism.

Approach to Pain Management in Osteoporosis

Timely prevention, early diagnosis, and treatment of osteoporosis are paramount to maintaining the quality of life and preventing musculoskeletal pain. Several therapeutic approaches for osteoporotic pain management are needed, including nonpharmacological, pharmacological, and surgical treatment.

Nonpharmacological Therapy

Physical therapy has a beneficial effect on reducing chronic pain in osteoporosis. Physical therapy for the treatment of pain can take many different forms. These include mechanical stimuli in the form of massage physiotherapy, which can be applied locally to the affected area, thermal stimulation in the form of high or short-wave thermic waves, and electrical stimulation in the form of direct current and low-frequency electrical stimulation [22]. Yoga has demonstrated benefits for pain relief and enhancing physical and social well-being. Similarly, pilates exercises have been shown to improve bone mineral density and psychosocial well-being. Hence, evidence has shown that physical therapy has a beneficial effect in reducing chronic pain and enhancing the quality of life of osteoporotic patients [23]. Physical massage of Soft tissue has been reported as a pain-relieving modality and facilitates muscle activity and postural control [24]. A similar result was seen with physical exercise in improving muscle strength, balance, coordination, and fall risk; it also improves general well-being by improving circulation, sleep, social contact, and immunity [25, 26]. Fracture-related acute pain can be relieved by pain-reliving positioning, multiple times cryotherapy, while chronic pain can be relieved by mild thermal therapy [22]. Diathermic ultrasound improves tissue metabolism, in turn, induces hyperemia, increases tissue circulation, and increases the elasticity of soft tissue fibers, ultimately reducing pain [22]. Neuropathic pain can be reduced by short-term cryotherapy stimuli and low-frequency electrical stimulation by transcutaneous electrical nerve stimulation by reducing the neuro peptides secretion [27].

Acupuncture can be considered an alternative adjunctive therapy for pain relief in elderly patients with vertebral fractures [28]. Magnetic field therapy in extremely low-frequency pico tesla and milli tesla ranges has been tried with promising results for treating osteoporosis-related fractures [29, 30]. Pulsed electromagnetic field exposure has an analgesic and anti-nociceptive effect that is comparable to that of opioids, but the effect lasts for a shorter duration only [31].

Vibration effects have also improved osteoporosis pain, neuromuscular coordination, and physical fitness [32]. Cognitive-behavioral therapy also has been shown to relieve pain and improve self-control. It acts on the principle of separation of the sensory and emotional aspects of pain [33].

Pharmacological Therapy

World Health Organization has recommended that the choice of analgesics should not be determined only based on pain intensity but also by the type of pain [34]. Hence, an analgesic used for the pain management of osteoporotic fracture should be administered throughout the day at scheduled intervals according to the different drug formulations' half-life and duration of action. The drug should be easy to administer and customizable as per an individual’s need. Because osteoporosis is frequently observed in older individuals with numerous comorbidities, a multidimensional strategy and concurrent pharmacological treatments for these disorders should be kept in mind in advance to prevent any negative medication reactions [35]. All anti-osteoporosis drugs approved for the treatment affect bone metabolism and help restore the normal bone structure, ultimately affecting pain reduction [36].

Acetaminophen, NSAIDs, Selective COX-2 Inhibitors, and Opioids

A meta-analysis has shown that acetaminophen can be safely used for mild to moderate musculoskeletal pain management, but its role in chronic pain management is limited [37]. NSAIDs and selective COX-2 inhibitors can be used for short-term pain relief, but these drugs have poor control of the neuropathic pain component, which is the main reason for chronic pain [37]. When administered in high doses, NSAIDs and selective COX-2 inhibitors raise the risk of thromboembolic events in patients with pre-existing cardiovascular disorders, raising questions about their safety. Diclofenac or selective COX-2 inhibitor use has been assessed to have a similar risk of an adverse cardiovascular event [38]. According to the current data, NSAIDs and COX inhibitors should be used to treat symptoms for the shortest amount of time and at the lowest effective dose [39].

On the other side, opioids can be used for moderate to severe osteoporosis-related pain that is not well managed with the above drugs. They are not the first line of drugs for pain management and should be used for a shorter period with dose monitoring to limit the side effects [40]. WHO recommended weak opioids like tramadol for oral use and transdermal patches (buprenorphine, fentanyl) for continuous pain for patients with poor compliance with oral medication intake. Long-acting opioids can give more consistent pain relief and better tolerance. Hence, based on the patient’s needs, a tailored approach should be used for pain management depending on the requirements of the patients [41].

Vitamin D

In addition to improving proximal muscular function, vitamin D positively impacts osteoblastic activity, promotes dietary calcium absorption from the intestinal tract, and controls calcium metabolism and parathyroid hormone action. The incidence of falls, subsequent fractures, and pain decreases as skeletal function is improved [42].

Antiresorptive Drugs

Bisphosphonates

Bisphosphonates inhibit bone resorption and increase bone mass, preventing fractures [43]. Their ability to inhibit the production of neuropeptides (such as Substance-P), calcitonin gene-related peptides, and inflammatory cytokines (TNF-alpha) is thought to be the mechanism involved in pain control [44]. Bisphosphonates like alendronate, risedronate, ibandronate, and zoledronate are widely used for pain relief in osteoporosis therapy [44, 45].

Compared to calcium treatment alone, alendronate dramatically decreases pain and enhances the quality of life in postmenopausal women [46]. In postmenopausal women without vertebral fractures, risedronate improves quality of life and lessens pain [45]. Ibandronate effectively reduces bone pain and stiffness and enhances motor function orally or intravenously [47]. Patients with low back pain whose symptoms are not advised to be treated by physical therapy and other painkillers should get a single intravenous dosage of 5 mg zoledronic acid [48].

Denosumab

A monoclonal antibody and agonist to the human RANK-L receptor, denosumab is an antiresorptive medication that prevents the osteoclast's precursor from differentiating and performing its role. It has been recommended for postmenopausal women with a high risk of fragility fractures [49]. There is little proof that denosumab works to relieve osteoporosis-related chronic pain. After 12 months of treatment, patients may have pain reduction; after 12 months, osteoporotic patients' lumber spine and hips have increased bone mineral density [50].

Teriparatide

Teriparatide is an anabolic medication that lowers back pain in osteoporosis patients and lowers the risk of vertebral and hip fractures [6, 51]. Teriparatide treatment in severe osteoporosis has demonstrated a reduction in back pain associated with vertebral fracture, disability, and increased quality of life improvement; however, a clinically significant benefit can be observed after 12 months of treatment [8]. Teriparatide prevents new-onset microfractures, accelerates fracture healing, stabilizes the fractured vertebra, and relieves pain [8, 52]. According to the evidence, compared to placebo, HRT, or alendronate, teriparatide had a lower incidence of new onset or worsening back pain [52, 53]. Moreover, teriparatide significantly increases bone mineral density, reflected in the T-score, improves life quality, and decreases the need for NSAIDs [54].

Calcitonin

Acute pain in osteoporosis is treated with calcitonin, an endogenous polypeptide hormone that suppresses bone resorption. When osteoporosis pain persists, calcium supplementation has been used as an analgesic with a 6–12 week cessation period [55]. According to a recent systematic evaluation of randomized-control studies, salmon calcitonin effectively reduces vertebral fracture pain after 1 week of treatment [56]. This data was previously corroborated by reviews [57, 58]. Furthermore, calcitonin is not advised for long-term osteoporosis therapy and is not effective in treating persistent back pain associated with osteoporosis and old vertebral fragility fractures [59, 60].

Strontium Ranelate

Strontium ranelate increases bone mineral density, dramatically lowers pain, and significantly lowers the frequency of vertebral and nonvertebral fragility fractures [61]. Strontium ranelate relieves pain after several months of treatment, speeds up the healing of fractures, and reduces the need for medicines [62]. In postmenopausal women, long-term treatment with strontium ranelate lowers the risk of fractures with minimal side effects. Patients who are susceptible to venous thromboembolism should exercise caution [63].

Selective estrogen receptor modulators (SERMs)

Commonly used SERMs are raloxifene and bazedoxifene; studies have shown that raloxifene can relieve osteoporosis pain and reduce analgesic use [64, 65].

Surgical Management

Percutaneous vertebroplasty is the most commonly used surgical procedure in osteoporosis due to fragility fracture. However, its superiority over nonoperative treatment in the relief of pain and quality of life improvement is debatable in women aged ≥ 60 years [66]. However, a recent systematic review showed significant, sustained pain relief and better functional outcomes for percutaneous cement augmentation of vertebra in the short and long term against conservative management [67]. Another surgical management used is hip arthroplasty, which showed good results with both cemented and uncemented femoral implants; however, the uncemented implant has shown a higher incidence of periprosthetic fracture [68, 69]

Conclusion

Single modalities of treatment for pain management of osteoporotic fragility fracture are not convincible. A combined nonpharmacological with pharmacological therapies combined with anti-fracture agents along with non-invasive analgesics should be considered. Physical therapy to improve axial stability should be initiated, and a customized exercise program should be introduced according to the patient’s needs to alleviate pain. Analgesics should be considered in the step ladder pattern for pain management, starting from NSAID and COX-2 inhibitors to weak opioids to strong opioids. For fragility vertebral fractures, cement vertebroplasty can be considered if conservative management fails or is contraindicated.

Author Contributions

All the above-mentioned authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted.

Funding

None.

Availability of Data and Materials

No repositories were used for data.

Declarations

Conflict of Interest

The authors declare no competing interests.

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