Регулирование причиняемой раком боли в хосписе и паллиативном уходе.

INTRODUCTION

Bone metastasis is among the most common complications of advanced malignancy and represents a major source of suffering in hospice and palliative care. Patients with multiple myeloma, breast cancer, and prostate cancer have particularly high rates of skeletal involvement [ 1 , 2 ]. In advanced cancer, pain related to bone metastasis is one of the most common and burdensome manifestations requiring palliative intervention [ 3 , 4 ]. From a clinical standpoint, cancer-induced bone pain (CIBP) is not simply a localized nociceptive complaint. It is frequently associated with impaired mobility, sleep disturbance, emotional distress, fear of movement, caregiver burden, and potentially life-threatening complications, such as pathologic fracture, malignant spinal cord compression, and hypercalcemia [ 3 , 4 ]. The syndrome is further complicated by the coexistence of persistent background pain and movement-evoked breakthrough pain, the latter of which may be severe despite otherwise adequate pain control at rest. In hospice populations, treatment decisions must also account for frailty, renal dysfunction, delirium vulnerability, swallowing difficulty, polypharmacy, and limited prognosis. These considerations make a purely disease-oriented approach insufficient. Instead, the management of CIBP requires an integrated approach that incorporates pathophysiology, symptom assessment, supportive care principles, and practical bedside decision-making. Accordingly, the present review provides a concise but clinically focused overview of the epidemiology, assessment, and management of CIBP, with particular attention to therapeutic proportionality and goal-concordant care in hospice practice.

EPIDEMIOLOGY AND CLINICAL SIGNIFICANCE

Bone is the third most common metastatic site after the lungs and liver, and skeletal dissemination is especially prevalent in tumors with prolonged disease trajectories [ 2 , 4 ]. Approximately 80% of patients with multiple myeloma, 65% to 75% of those with breast cancer, and 60% to 70% of those with prostate cancer develop bone metastases during the course of their illness [ 1 , 2 ]. Clinically meaningful skeletal involvement is also observed in lung, renal, and thyroid malignancies. Among patients with metastatic bone disease, pain is highly prevalent; in one cohort, 91.6% of patients with bone metastases reported pain [ 5 ], and registry data from inpatient palliative care showed that more than half of patients had moderate to severe pain at admission [ 3 ]. The clinical importance of CIBP lies not only in its prevalence but also in its consequences. Pain from bone metastasis can restrict mobility, reduce self-care capacity, impair nutritional intake, and accelerate social dependency. Recurrent incident pain during transfers or weight bearing may result in anticipatory immobility, which in turn promotes deconditioning, pressure injuries, increases the risk of venous thromboembolism, and diminishes dignity. Skeletal-related events, including pathologic fracture, bone surgery, radiotherapy to bone, spinal cord compression, and hypercalcemia, impose additional morbidity and often precipitate unplanned hospital transfers [ 6 ]. Importantly, pathologic fracture is associated with reduced survival and substantial deterioration in quality-of-life [ 6 ]. For these reasons, CIBP should be viewed as a multidimensional clinical syndrome that influences prognosis, place of care, caregiver burden, and the overall trajectory of end-of-life care rather than as an isolated symptom amenable to uniform analgesic escalation.

PATHOPHYSIOLOGY

The pathophysiology of CIBP is complex, dynamic, and heterogeneous. The classic “seed-and-soil” paradigm explains why malignant cells preferentially colonize bone, where the stromal environment, extracellular matrix, and local growth factors provide a supportive niche for tumor survival and proliferation [ 4 , 7 ]. Once metastasis is established, reciprocal interactions among tumor cells, osteoclasts, osteoblasts, stromal cells, and immune mediators generate a self-amplifying cycle of structural injury and nociceptive activation. In many solid tumors, osteoclast-mediated bone resorption is a key event. Osteoclasts acidify the resorption lacuna, and the resulting acidic microenvironment activates nociceptive ion channels such as transient receptor potential vanilloid 1 and acid-sensing ion channels on primary afferent fibers [ 8 , 9 ]. Tumor and inflammatory cells also release interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, prostaglandin E2, endothelin-1, and nerve growth factor, which sensitize peripheral nociceptors and lower activation thresholds [ 8 , 9 ]. The RANKL/RANK/OPG axis has particular relevance because increased RANKL signaling promotes osteoclast differentiation and bone destruction, thereby linking tumor biology directly to pain generation and skeletal-related events [ 10 ]. Repetitive peripheral input subsequently induces central sensitization within the spinal dorsal horn through glutamatergic transmission and N-methyl-D-aspartate receptor activation, producing wind-up, hyperalgesia, and movement-evoked pain that may be disproportionate to the immediate structural stimulus [ 11 ]. In some patients, neural injury or compression contributes a neuropathic component characterized by burning, electric shock-like pain, or allodynia. The overall clinical phenotype is therefore best understood as a mixed pain syndrome incorporating inflammatory, nociceptive, neuropathic, and centrally amplified elements. Recognition of this mechanistic diversity is essential because it explains why monotherapy is often inadequate and why mechanism-informed combinations of opioids, adjuvant analgesics, bone-targeted agents, and local treatments may be required.

CLINICAL ASSESSMENT

The assessment of CIBP should begin with careful characterization of the temporal pattern, provoking factors, and functional impact. Background pain is typically a persistent deep ache present at rest, whereas breakthrough pain is abrupt, severe, and often triggered by movement, transfer, coughing, or weight bearing [ 5 , 12 ]. Distinguishing these patterns is clinically important because breakthrough incident pain often necessitates anticipatory rescue dosing, mechanical support, or local intervention rather than simple escalation of scheduled opioids. Standard tools such as the numeric rating scale, visual analogue scale, and Brief Pain Inventory are useful for documenting symptom burden and monitoring responses; however, numerical intensity should be interpreted within a broader framework. Clinicians should assess pain location, radiation, quality, onset, relieving factors, sleep disruption, mood effects, and the degree to which pain interferes with mobility, toileting, and family interaction. Neuropathic descriptors, including burning, tingling, electric shock-like sensations, and allodynia, may identify patients more likely to benefit from adjuvant agents [ 13 ]. Cognitive impairment, delirium, or advanced frailty may require the use of observational tools and collateral information from family or bedside staff. Imaging should be goal-directed and proportionate. Plain radiography may reveal cortical destruction or fracture risk, computed tomography is often useful for structural clarification, and magnetic resonance imaging is the modality of choice when malignant spinal cord compression is suspected [ 14 ]. Red flag features include rapidly worsening back pain, new weakness, sensory change, gait deterioration, and bladder or bowel dysfunction. In addition, assessment should include renal function, hepatic status, swallowing ability, constipation burden, prior opioid exposure, and overall prognosis, because these factors directly influence drug selection, route of administration, and the appropriateness of disease-modifying interventions.

PHARMACOLOGICAL MANAGEMENT

The World Health Organization analgesic ladder remains a practical framework, although hospice care often necessitates an earlier transition to strong opioids than a rigid stepwise model would imply [ 15 ]. The 2023 ASCO guideline recommends offering opioids to adults with moderate-to-severe cancer pain unless contraindicated, starting with the lowest effective dose of an immediate-release opioid and reassessing promptly based on analgesia, adverse effects, organ function, and prior opioid exposure [ 16 ]. Non-opioid agents such as acetaminophen and nonsteroidal anti-inflammatory drugs may benefit patients with inflammatory components of bone pain and may reduce opioid requirements, although their use is frequently constrained by renal impairment, gastrointestinal bleeding risk, thrombocytopenia, or cardiovascular comorbidity. For moderate to severe background pain, strong opioids remain the cornerstone of treatment. Morphine is widely used, but hydromorphone, oxycodone, and fentanyl may be preferable when renal dysfunction, swallowing difficulty, or neurotoxicity complicates therapy [ 16 ]. Scheduled dosing should be accompanied by breakthrough medication, and titration should be based on total rescue use, tolerability, and repeated reassessment rather than isolated pain scores. Breakthrough doses are commonly individualized at approximately 5% to 20% of the total daily opioid requirement, and constipation prophylaxis, antiemetic support, and surveillance for sedation or delirium are integral to safe opioid practice [ 16 ]. Opioid rotation becomes particularly valuable when analgesia is incomplete or adverse effects are disproportionate to the opioid dose. Breakthrough incident pain deserves separate consideration because increasing the background opioid dose alone may worsen sedation without adequately controlling short, movement-related pain flares [ 12 ]. Predictable episodes may respond better to preemptive rescue doses before care activities, judicious use of rapid-onset fentanyl formulations where available, and concurrent non-pharmacological support such as transfer assistance or bracing. As summarized in Table 1 , pharmacological options for CIBP should be selected according to the dominant pain mechanism, expected time to benefit, route feasibility, and adverse-effect profile within the hospice setting. Adjuvant analgesics should be chosen according to the underlying mechanism and symptom phenotype. Corticosteroids may reduce pain associated with inflammatory edema, capsular stretch, or neural compression, and they can also improve appetite and energy in selected patients [ 17 ]. Gabapentinoids may be considered when neuropathic features are prominent, although dizziness and somnolence can exacerbate fall risk and cognitive impairment [ 13 ]. Ketamine may be considered in highly selected patients with refractory pain or opioid tolerance; however, the clinical evidence remains limited and heterogeneous, with mixed trial results and only modest short-term benefit reported in some systematic reviews and clinical studies [ 18 , 19 ]. Bone-modifying agents also have an established role. Pamidronate and zoledronic acid reduce osteoclast-mediated skeletal complications, whereas denosumab targets RANKL directly and has demonstrated superiority to zoledronic acid in reducing skeletal-related events in comparative analyses [ 20 - 22 ]. In hospice settings, however, the decision to initiate or continue these therapies should take into account expected survival, time to benefit, treatment burden, venous access, cost, renal function, and the patient’s preferences. The most appropriate pharmacological strategy should therefore be individualized, regularly reassessed, and adjusted according to functional goals and the anticipated disease trajectory.

RADIOTHERAPY AND OTHER NON-PHARMACOLOGICAL INTERVENTIONS

External beam radiation therapy is a standard and effective local treatment for painful bone metastases and remains especially valuable when pain is focal, opioid escalation is limited by toxicity, or incident pain reflects mechanical provocation from a discrete lesion [ 23 ]. The 2024 ASTRO guideline recommends conventional palliative regimens such as 8 Gy in 1 fraction, 20 Gy in 5 fractions, 24 Gy in 6 fractions, or 30 Gy in 10 fractions for symptomatic bone metastases; regimen selection should be guided by prognosis, logistics, prior irradiation, spinal involvement, and patient goals [ 23 ]. Both single-fraction and multifraction regimens achieve meaningful palliation, with overall response rates commonly approaching 70% to 80% [ 23 ]. For patients with limited prognosis or difficulty traveling, a single 8 Gy fraction is often particularly attractive because it minimizes logistical burden while preserving analgesic efficacy. Re-irradiation may be appropriate for recurrent pain after an initial response. Stereotactic body radiotherapy (SBRT) can provide higher complete response rates and more durable local control in carefully selected patients, particularly those with spinal metastases, good performance status, and anticipated survival of several months [ 24 ]. Nonetheless, SBRT requires precise immobilization, planning, and the capacity to travel, factors that may render it unsuitable for many hospice patients. For selected patients with impending or established pathologic fracture, orthopedic stabilization or other interventional treatments may also help preserve function and facilitate safer mobilization when consistent with prognosis and goals of care [ 6 , 25 ].

Non-pharmacological supportive strategies should be integrated early rather than reserved as measures of last resort. Bracing, mobility aids, pressure redistribution, transfer training, and caregiver education can reduce incident pain and fracture risk. Physical and occupational therapy adapted to prognosis may preserve safe function, while massage, relaxation techniques, music therapy, and other supportive modalities may lessen distress even when direct analgesic effects are modest. In hospice practice, these interventions are particularly important because they can improve comfort, confidence, and dignity without imposing substantial additional toxicity.

HOSPICE-SPECIFIC CONSIDERATIONS

Management decisions in hospice must remain explicitly goal-concordant. The relevant question is not merely whether an intervention can reduce pain under ideal circumstances, but whether it can achieve meaningful relief with a burden acceptable to the patient and family. Conversion from oral to parenteral regimens should be performed carefully, with explicit rescue orders and ongoing monitoring for sedation, myoclonus, delirium, and secretion burden. Suspected malignant spinal cord compression or severe hypercalcemia still warrants prompt assessment and discussion, yet the intensity of intervention should reflect anticipated reversibility, likely benefit, and the patient’s wishes regarding hospitalization or transfer [ 13 , 26 ]. Pathologic fracture risk should also be considered proactively. Attention to positioning, movement planning, and family education can help prevent severe pain exacerbations.

Another distinctive feature of hospice care is the centrality of communication. Patients may fear that escalating pain signifies imminent death, while families may assume that reduced mobility could be prevented simply be increasing medication. Sensitive explanation of the mechanisms of incident pain, the rationale for rescue medication, and the limits of pharmacological therapy can reduce anxiety and improve adherence. Finally, Saunders’ concept of total pain remains highly relevant [ 27 ]. Psychological distress, loss of role, social isolation, caregiver guilt, and existential suffering can intensify pain perception and shape the experience of analgesic success or failure. Consequently, multidisciplinary management involving physicians, nurses, pharmacists, rehabilitation professionals, social workers, and spiritual care providers is not an optional enhancement but a core component of high-quality hospice care for CIBP.

CONCLUSION

Cancer-induced bone pain is among the most challenging pain syndromes encountered in hospice and palliative care because it reflects interrelated structural, inflammatory, neuropathic, and centrally sensitized mechanisms. Its clinical expression extends beyond pain intensity to include immobility, caregiver burden, skeletal emergencies, and existential distress. Optimal management therefore requires more than routine opioid escalation. It depends on systematic assessment of background and breakthrough pain, appropriate use of strong opioids and rescue medication, mechanism-oriented adjuvant therapy, consideration of bone-modifying agents, timely radiotherapy when feasible, and practical supportive strategies that reduce movement-related suffering. Above all, treatment must remain proportional to prognosis and closely aligned with the patient’s goals of care. A mechanism-based, multidisciplinary, and patient-centered approach offers the best opportunity to relieve suffering while preserving dignity and comfort during the final phase of life.

SUPPLEMENTARY MATERIALS

Supplementary materials can be found via https://doi.org/10.14475/jhpc.2026.29.3.146 .