The incidence of chronic pain is estimated to be 20–25% worldwide. Although major improvements in pain control have been obtained, more than 50% of the patients reports inadequate relief. It is accepted that chronic pain, if not adequately and rapidly treated, can become a disease in itself, often intractable and maybe irreversible. This is mainly due to neuroplasticity of pain pathways. In the present review I will discuss about pain depicting the rational for the principal pharmacological interventions and finally focusing on opioids, that represent a primary class of drug to treat pain.
chronic pain; opioids; tapentadol; multi-target pharmacology
Bone pain is one of the most frequent kinds of chronic pain, mainly in elderly patients. It causes a significant worsening of functional capacity and deterioration in the quality of life in people affected. Mechanisms of pain in osteoporosis are poorly known and often extrapolated by other pathologies or other experimental model. One of principal causes would be a “hyper-remodeling” of bone, that involves osteoclasts activity and pathological modifications of bone innervation. Several studies show that osteoclasts play a significant role in bone pain etiology.
Pain in osteoporosis is mainly nociceptive, if it become persistent a sensitization of peripheral and central nervous system can occur, so underlining the transition to a chronic pain syndrome. Central sensitization mechanisms are complex and involve several neuromediators and receptors (Substance P, NMDA, etc.).
Most common manifestations of osteoporosis are vertebral compression fractures that cause persistent pain, though to differentiate from pain originating in structures as joint or muscle. First manifestation can be an acute pain due to pathological fracture, those of hip often causes disability.
Pain in osteoporosis is an important clinical challenge. Often its complications and consequences on patient quality of life are underestimated with not negligible social implications.
A balanced and early multimodal pain therapy including opioids as necessary, even in cases of acute pain, improve the functional capacity of patients and helps to prevent neurological alterations that seems to contribute in significant way in causing irreversible pain chronic syndromes.
chronic pain; bone innervation; osteoclasts activity; opioids
The prevalence of osteoporosis increases markedly with age: currently it is estimated that over 200 million people suffer from osteoporosis worldwide. One of the most feared and more frequent complications of osteoporosis is pain, which affects 85% of patients. Commonly in the treatment of chronic pain the therapeutic strategy is based on a three-ladder approach, involving opioids for moderate and severe pain. As proposed by the World Health Organization (WHO), according to the intensity of chronic pain, analgesic treatment can be established. Despite the debate and updates to the analgesic ladder for pain published in 1986 by the WHO, the benefits resulting from its worldwide use are uncontested. In case the pain was not responsive to drugs of pain ladder, is necessary to resort to specialized practices (e.g. subarachnoid infusion of drugs). The oral route for administering analgesics should be preferred, provided that the patients are able to use it. About 50% of all opioid users experience at least one side effect, and more than 20% discontinued treatment due to a serious adverse event. Despite published guidelines and WHO’s pain ladder for the management of chronic pain, the treatment of this condition remains suboptimal. Given the physiopsychopathology and complexity of the problems of chronic osteoporotic pain, a multimodal and multidisciplinary approach is still considered the best way to diagnose and treat this disease.
chronic pain; bone pain; opioids; osteoporosis
Sarcopenia is a condition characterized by loss of skeletal muscle mass and function. Although it is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength and it is strictly correlated with physical disability, poor quality of life and death. Risk factors for sarcopenia include age, gender and level of physical activity. In conditions such as malignancy, rheumatoid arthritis and aging, lean body mass is lost while fat mass may be preserved or even increased. The loss in muscle mass may be associated with increased body fat so that despite normal weight there is marked weakness, this is a condition called sarcopenic obesity. There is an important correlation between inactivity and losses of muscle mass and strength, this suggests that physical activity should be a protective factor for the prevention but also the management of sarcopenia. Furthermore one of the first step to be taken for a person with sarcopenia or clinical frailty is to ensure that the sarcopenic patient is receiving correct and sufficient nutrition. Sarcopenia has a greater effect on survival. It should be important to prevent or postpone as much as possible the onset of this condition, to enhance survival and to reduce the demand for long-term care. Interventions for sarcopenia need to be developed with most attention on exercise and nutritional interventions.
sarcopenia; epidemiology; weakness; sarcopenic obesity
Sarcopenia is an age-related process of skeletal muscle loss associated with declining physical performance, highly prevalent among older subjects, with a negative prognostic effect on falls, disability and mortality risk. Modern approaches to sarcopenia case finding and diagnosis are based on physical performance measures, while assessment of muscle mass represents the second diagnostic step. Muscle mass can be quantified at different levels of body composition, with a complexity increasing from atomic detection to anatomic measure. In the choice of measuring method, different factors have to be taken into account, including validity, simplicity, cost and specific purpose (clinical versus research). Some methods, such as MRI and CT, have high validity but are complex and costly. Bioelectrical impedance analysis is inexpensive and easy to perform in most settings, being the preferred method for clinical practice. Dual energy X-ray absorptiometry has intermediate cost and complexity with good reproducibility, and is more reliable for research setting. Other methods, such as administration of tritium (D3)-marked creatine and measurement of urinary D3-creatinine, are still in a preclinical phase of development. For all methods the issue of normative data does exist and needs to be solved, in order to reliably identify homogeneous populations with sarcopenia, to be targeted in clinical practice and intervention studies.
sarcopenia; skeletal muscle; physical performance; elderly; diagnostic methods
Metabolic disturbances of bone are frequent in patients with chronic liver disease. The prevalence of osteoporosis among patients with advanced chronic liver disease is reported between 12% and 55%; it is higher in primary biliary cirrhosis. All patients with advanced liver disease should be screened for osteoporosis with a densitometry, especially if the etiology is cholestatic and in the presence of other risk factors. Clinical relevance of hepatic osteodystrophy increases after liver transplantation. After liver transplant, a rapid loss of bone mineral density can be detected in the first 6 months, followed by stabilization and slight improvement of the values. At the time of transplantation, bone density values are very important prognostic factors.
Therapy of hepatic osteodystrophy is based primarily on the control of risk factors: cessation of tobacco and alcohol assumption, reduction of caffeine ingestion, exercise, supplementation of calcium and vitamin D, limitation of drugs such as loop diuretics, corticosteroids, cholestyramine.
Bisphosphonates have been proposed for the therapy of osteoporosis in patients with liver disease, particularly after liver transplantation. The possible side effects of oral administration of bisphosphonates, such as the occurrence of esophageal ulcerations, are of particular concern in patients with liver cirrhosis and portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured esophageal varices, although this risk is probably overestimated.
hepatic osteodystrophy; liver cirrhosis; liver transplantation; vitamin D
The prophylaxis of venous thromboembolism (VTE) with anticoagulant drugs is a long-established practice in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures, while there are few data regarding the prevention of VTE in other fields of orthopaedic surgery and traumatology. In order to provide practical recommendations for daily management of VTE prophylaxis in orthopaedic patients, recently the Italian Societies of Thrombosis and Haemostasis, Orthopaedics and Traumatology and Anaesthesia have drawn up a first Intersociety Consensus on antithrombotic prophylaxis in total hip and knee replacement surgery, and in the treatment of femoral neck fracture, then updated in 2013, and a subsequent Intersocietary Consensus, in cooperation also with the Society of general practitioners, concerning antithrombotic prophylaxis in other types of orthopaedic surgery and traumatology. Before starting any prophylactic treatment it is of crucial importance the assessment of both thrombotic and bleeding risk of patients undergoing surgery. Thromboembolic prophylaxis is recommended with low molecular weight heparins (LMWH), fondaparinux (FON) or with the new oral anticoagulants (NOA) in patients undergoing hip and knee replacement surgery while patients undergoing treatment of femoral neck fracture should be treated with LMWH or FON. Regarding the non-prosthetic orthopaedic surgery and traumatology, it is recommended prophylaxis with LMWH or FON in situations of high thromboembolic risk or in the case of interventions or trauma involving pelvis, acetabulum or knee.
prevention of venous thromboembolism; total hip replacement; total knee replacement; femoral neck fractures; anticoagulant prophylaxis
The third proximal femur fractures are divided into medial and lateral ones. For medial fractures already exists unanimity of thought for the choice of treatment that involves the prosthetic replacement of the hip joint in patients over 60 without indications to the synthesis. Regarding the lateral femur fractures this unanimity does not exist yet even if the majority of surgeons practice treatment with osteosynthesis. We want to highlight if there are any types of lateral fractures associated with patient’s clinical condition in which it might be more useful to a prosthetic replacement with the aim of being able to allow a total load and earlier deambulation, reducing complications related to a possible patient immobilization.
lateral femoral fracture; hip replacement; earlier deambulation
Risedronate is a heterocyclic orally active aminobisphosphonate and it belongs to the bisphosphonate category: these drugs are powerful bone resorption inhibitors, thanks to their affinity for hydroxyapatite crystals at bone mineral matrix level and to their inhibiting effects on osteoclast activity, using the ability of inhibiting enzyme FPPS. Recent observations have reported that risedronate can decrease resorption entity, not only of the trabecular bone, but also of the cortical bone, modifying therefore the (bone compact) thickness and the cortical porosity entity, which is largely responsible of femoral fracture especially among elderly patients. Various controlled studies have proved the efficacy of risedronate in reducing fragility fracture risk significantly. In particular, it is able to lower in a very significant way the incidence of vertebral, non-vertebral and femoral fractures, with precocity of effects after only six months of therapy. The extension of protocols, moreover, has marked its efficacy even after seven years of treatment. Under the metabolic profile, these studies have also shown that risedronate activity can reduce bone resorption markers and increase bone density values at lumbar and femoral level. Results emerged from a group of women aged over 80 are relevant: risedronate has proved capable of decreasing femoral fracture risk. Also in male and steroidal osteoporosis, clinical controlled studies have shown that risedronate is effective in decreasing vertebral fracture incidence. Lastly, tolerability: the main side effects concern the gastrointestinal tract and they are usually rare, of minor entity and can be solved by sospending the treatment. Acute phase reaction is rare, due to risedronate oral administration; it is also valid for osteonecrosis of the jaw and atypical fractures.
osteoporosis; bisphosphonates; risedronate; fractures; osteoclasts
Sarcopenia is the age-associated loss of skeletal muscle mass and function. It is a major clinical problem for older people and research in understanding of pathogenesis, clinical consequences, management, and socioeconomic burden of this condition is growing exponentially. The causes of sarcopenia are multifactorial, including inflammation, insulin resistance, changing endocrine function, chronic diseases, nutritional deficiencies and low levels of physical activity. Operational definition of sarcopenia combines assessment of muscle mass, muscle strength and physical performance. The diagnosis of sarcopenia should be based on having a low appendicular fat free mass in combination with low handgrip strength or poor physical functioning. Imaging techniques used for estimating lean body mass are computed tomography, magnetic resonance imaging, bioelectrical impedance analysis and dual energy X-ray absorptiometry, the latter considered as the preferred method in research and clinical use.
Pharmacological interventions have shown limited efficacy in counteracting the age-related skeletal muscle wasting. Recent evidence suggests physical activity and exercise, in particular resistance training, as effective intervention strategies to slow down sarcopenia.
The Italian Society of Orthopaedics and Medicine (Or-toMed) provides this position paper to present the update on the role of exercise on sarcopenia in the elderly.
physical exercise; sarcopenia; physical activity
Falls in the elderly are a public health problem. Consequences of falls are increased risk of hospitalization, which results in an increase in health care costs. It is estimated that 33% of individuals older than 65 years undergoes falls. Causes of falls can be distinguished in intrinsic and extrinsic predisposing conditions. The intrinsic causes can be divided into age-related physiological changes and pathological predisposing conditions. The age-related physiological changes are sight disorders, hearing disorders, alterations in the Central Nervous System, balance deficits, musculoskeletal alterations. The pathological conditions can be Neurological, Cardiovascular, Endocrine, Psychiatric, Iatrogenic. Extrinsic causes of falling are environmental factors such as obstacles, inadequate footwear. The treatment of falls must be multidimensional and multidisciplinary. The best instrument in evaluating elderly at risk is Comprehensive Geriatric Assessment (CGA). CGA allows better management resulting in reduced costs. The treatment should be primarily preventive acting on extrinsic causes; then treatment of chronic and acute diseases. Rehabilitation is fundamental, in order to improve residual capacity, motor skills, postural control, recovery of strength. There are two main types of exercises: aerobic and muscular strength training. Education of patient is a key-point, in particular through the Back School. In conclusion falls in the elderly are presented as a “geriatric syndrome”; through a multidimensional assessment, an integrated treatment and a rehabilitation program is possible to improve quality of life in elderly.
falls; elderly; multidimensional assessment; comprehensive geriatric assessment
The application of Dual-energy X-ray absorptiometry (DEXA) in orthopaedic surgery gradually has been extended from the study of osteoporosis to different areas of interest like the study of the relation between bone and prosthetic implants. Aim of this review is to analyze changes that occur in periprosthetic bone after the implantation of a total hip arthroplasty (THA) or a total knee arthroplasty (TKA). In THA the pattern of adaptive bone remodeling with different cementless femoral stems varies and it appears to be strictly related to the design and more specifically to where the femoral stem is fixed on bone. Short stems with metaphyseal fixation allow the maintenance of a more physiologic load transfer to the proximal femur decreasing the entity of bone loss. Femoral bone loss after TKA seems to be related to the stress shielding induced by the implants while tibial bone remodeling seems to be related to postoperative changes in knee alignment (varus/valgus) and consequently in tibial load transfer. After both THA and TKA stress shielding seems to be an inevitable phenomenon that occurs mainly in the first year after surgery.
dual-energy X-ray absorptiometry; adaptive bone remodeling; total hip arthroplasty; total knee arthroplasty
We report the clinical outcome of an elderly man with knee osteoarthritis (OA) accompanied with recurring severe joint pain. He had no history of trauma to the affected knee. Plain radiographs and magnetic resonance imaging uncovered rapid and severe bone deformity, which likely led to the patient’s progressed radiographic OA. These findings indicate that a pathophysiology of OA may be bone alterations.
knee; osteoarthritis; rapid bone destruction
Osteoporosis is a highly prevalent condition characterized by decreases in bone mass and microarchitectural alterations. Bone fractures, especially of the hip and vertebrae, are the most burdensome complications of osteoporosis, being associated with high risk of disability, institutionalization and mortality. The detection of osteoporosis relies on the quantification of bone mineral density via imaging techniques such as dual-energy X-ray absorptiometry. However, therapeutic decision-making should be based on a comprehensive fracture risk assessment, which may be obtained through validated algorithms. Once the decision of treating has been taken, non-pharmacological strategies should be implemented together with the prescription of anti-osteoporotic agents. Numerous drugs are currently available to treat osteoporosis and the choice of a specific compound should be guided by efficacy and safety considerations. The present review provides a concise synopsis of the current evidence in the management of osteoporosis, from screening to drug prescription. Novel anti-osteoporotic agents are also briefly presented.
vitamin D; denosumab; bisphosphonates; teriparatide; strontium ranelate
Fragility fractures are the most severe complications of osteoporosis and the poor mechanical properties of bone can make fixation and healing of these fracture extremely difficult. The role of orthopaedic surgeons does not end in skillful fixation of the fractures, but they have the unique opportunity to prevent complications which can negatively affect the patient’s quality of life. The best practice for preventing the risk of further fractures in patients presenting fragility fractures includes fall prevention, investigation of possible causes underlying osteoporosis, attention to exercise, calcium and vitamin D supplementation as well as prescription of drugs. Actually two classes of agents can be used for their effect on fracture prevention: antiresorptive and bone forming agents. Systemic therapy reduces the risk of vertebral (30–70%) and non-vertebral fractures (12–53%), depending on agents and patients’ compliance.
Preclinical and clinical studies have shown that pharmacological agents involved in osteoporosis can also influence the phases of fracture repair. Preclinical studies and evidences from case reports showed a positive effect of anabolic drugs on bone healing and implant osseointegration.
The interventions in the process of fracture healing had evolved from a diamond to a pentagon concept, with interactions between the mechanical environment, the local therapies, the vascularity of the fracture site, the biology of the host and the systemic therapy which has the potential to represent the fifth interaction factor.
The orthopaedic surgeon plays a central role in clinical setting to evaluate the efficacy of systemic anti-fracture drugs for improving fracture repair and preventing complications.
anabolics; bisphosphonates; bone healing; fracture; osteoporosis; prevention
Breast cancer therapy after surgery has been improved in recent years. Adjuvant therapies like aromatase inhibitors are being extensively used among breast cancer survivors. This leaded to cancer related and iatrogenic osteoporosis. Management of these patients needs to be focused and differentiated from the standard age related osteoporosis in women. All guidelines consider mandatory to assess fracture risk periodically in all breast cancer survivors. Risk assessment diagnostic FRAX tool is the most used but it’s not born specifically for cancer related osteoporosis. The therapeutic management of this kind of osteoporosis has been studied by different societies. Since breast cancer survivors are at risk of osteopenia and osteoporosis, counseling regarding modifiable risk factors is mandatory and advocated. The beginning of the treatment should be tailored in each patient.
breast cancer; osteoporosis; women’s health; bone resorption; drug therapy
A variety of genetic and environmental factors contribute to the progressive develop of OA. It is necessary to identify people who are developing initial changes in cartilage and/or subchondral bone before onset of classical radiological features in order to detect early phase of OA. Recent quantitative MRI techniques can evaluate the structural, mechanical and biochemical characteristics of cartilage. T2 mapping is able to assess cartilage volume and defects measurement, delayed gadolinium enhanced MRI (dGEMRIC) and Contrast Enhanced Computed Tomography (CECT) can reveal Cartilage GAG content. Accurate and reliable serum, urine and synovial fluid biomarkers are also requested. Several biomarkers have been studied and proposed, but there are many critical issues to consider for inferring useful data from studies on biomarkers in early OA such as phase of disease, specific joint sites, systemic concentrations, circadian rhythm, their clearance from the joint, etc. Recently proteomics has produced great expectations to improve the early diagnosis of OA. These discoveries may open opportunities for the identification of early stage of OA leading to manage the symptoms and ultimately slow the progression of OA.
early osteoarthritis; imaging; biomarker
Several evidences have shown in the last years a possible correlation between cardiovascular diseases and osteoporosis. Patients affected with osteoporosis, for example, have a higher risk of cardiovascular diseases than subjects with normal bone mass. However, the heterogeneous approaches and the different populations that have been studied so far have limited the strength of the findings. Studies conducted in animal models show that vascular calcification is a very complex mechanism that involves similar pathways described in the normal bone calcification. Proteins like BMP, osteopontin, osteoprotegerin play an important role at the bone level but are also highly expressed in the calcified vascular tissue. In particular, it seems that the OPG protect from vascular calcification and elevated levels have been found in patients with CVD. Other factors like oxidative stress, inflammation, free radicals, lipids metabolism are involved in this complex scenario. It is not a case that medications used for treating osteoporosis also inhibit the atherosclerotic process, acting on blood pressure and ventricular hypertrophy. Given the limited amount of available data, further studies are needed to elucidate the underlying mechanisms between osteoporosis and cardiovascular disease which may be important in the future also for preventive and therapeutic approaches of both conditions.
osteoporosis; cardiovascular disease; vascular calcification
Osteoporotic fractures became the most important cause of disability and an increasing burden to the public health costs in Italy and in many regions of the world. Health professionals play a central role in identifying people at high risk of osteoporosis and osteoporotic fractures. However it is important to have available methods that allow to identify patients showing high risk of fragility fractures, with lower costs and high sensitivity than those currently adopted, e.g. Dual Energy X-ray Absorptiometry (DEXA).
The computer-based algorithm (FRAX®) developed by WHO shows some barriers in primary care, for instance the difficulty to access this tool by General Practitioners (since it is not available in their DATABASE). Moreover, since the incidence of fracture and the prevalence of associated risk factors change over time, risk prediction algorithms need to be dynamic, so that they can be remodelled over time. In Italy, the Health Search - CSD Longitudinal Patients Database (HSD) could potentially provide the data needed to support the development and validation of an applicable prediction tool in primary care.
In this framework we aim to develop and validate a prognostic score for osteoporotic fractures in Italian General Practice and to establish a risk map.
osteoporosis; fractures; prevention; Health Search Database (HSD); FRAX
Since low adherence to a long-term therapy results in a poor clinical outcome and significantly increases healthcare costs, adherence to the treatment of chronic disorders is an issue of great interest. This is particularly true of the treatment of osteoporosis (OP).
Purpose of study
Adherence to the osteoporosis therapy in patients treated with bisphosphonates in tablet form has been evaluated in comparison with the adherence of those taking alendronate in soluble solution.
Methods and materials
Here we present a retrospective study of 245 patients treated with alendronate, risedronate and ibandronate tablets and a prospective study of 118 patients treated with soluble alendronate. In both studies, patients have been observed for a period of 12 months.
The analysis of patients’ persistence with the treatment plan, assessed at three, six and 12 months, revealed a significantly higher adherence (p < 0.005) in the cohort of patients treated with soluble alendronate (92.37% at 12 months) compared with those who followed the course of treatment with tablets (65.4 %, 12 months).
The investigation showed higher adherence to the oral therapy with soluble alendronate, demonstrating that a formulation obtained by this method can contribute to a higher level of persistence with the treatment of a disease such as osteoporosis, which requires a long-term therapeutic plan.
adherence; soluble alendronate; bisphosphonate; compliance; osteoporosis
Treatment with bisphosphonates induces differentiation and activation of Vγ9Vδ2 T lymphocytes obtained from peripheral blood showing also an antitumoral effect in both in vitro and in vivo models. Aim of the present study was to determine in vivo the effect of BPs treatment in patients affected with osteoporosis on Vγ9Vδ2 T lymphocytes.
We have studied Vγ9Vδ2 T lymphocytes expansion and differentiation from PBMC obtained from osteoporotic patients treated with one of the following bisphosphonates zoledronate, alendronate, neridronate or risedronate.
We have found that zoledronic acid, followed by alendronate was the most effective on reducing CM population (100%) and increasing TEM and TEMRA γδ population.
Our results indicate that in vivo treatment with BPs induces Vγ9Vδ2 cells to mature toward the effector phenotype, which may induce more antiresorptive responses.
Vγ9Vδ2 T lymphocytes; osteoporosis; bisphosphonates
In the context of osteoporosis the presence of a fragility fracture (vertebral or non-vertebral) constitutes a condition of severe osteoporosis; the most common fractures due to this disease are the responsibility of the proximal femur (hip), spine and wrist representing one of the leading causes of disability in the elderly population, as well as one of the greatest contributions to health care costs. By analyzing a population of patients hospitalized at a rehabilitation ward for post-acute outcomes of hip fracture fragility it was able to observe the effectiveness of preventive intervention, the risk of vertebral fractures and the importance of comorbidity.
osteoporosis; risk of fracture; vertebral fracture
We describe three upper limb injuries admitted in one year to our institution resulting from falls from motorised mobility scooters (MMS) where all three users were novices, using their MMS for less than 6 weeks. They sustained injuries in close proximity to their homes, necessitating admission to hospital. None had received any formal training before commencing use of their respective devices. Use of MMS devices increases independence in mobility, enhances quality of life, improves self-esteem, facilitating social participation in everyday life. Use of these devices is not without risks, and no clear safety guidelines or competency testing exists for users. We believe these injuries in novice users highlights this deficiency, and should alert prescribers of these devices to advocate some form of driver training for new users.
motorised mobility scooters; fracture; elderly; trauma; orthopaedics; rehabilitation