Antimo Moretti

The contribution of cortical and trabecular tissues to bone strength: insights from denosumab studies.

All materials undergo an aging process which is characterized essentially by changes of the rigidity (stiffness), of the ability to absorb the stresses (toughness) and then ultimately in the mechanical resistance (strength). Both cortical and trabecular bone undergo a continuous process of structural remodeling with the main aim to preserve their biomechanical properties. An imbalance in this process, which promotes bone resorption, results in a quantitative loss of bone tissue and in a qualitative alteration of the skeletal microarchitecture, as you can see in osteoporosis, rheumatoid arthritis or bone metastases. Cortical component has a prominent role on strength therefore loss of cortical bone that is prevalent in elderly may explain the higher frequency of fractures of bones composed mainly of cortical bone such as the proximal femur. Remodeling inhibition with denosumab improved structural strength without altering material properties, that can be primarily explained by the combined effects of increased trabecular and cortical bone mass, and reductions in trabecular eroded surfaces and particularly cortical porosity. Denosumab for its mechanism of action and pharmacokinetics results in a significant, early and continued increase in BMD with enhanced bone strength improving both cortical and trabecular bone.

Are dietary supplements and nutraceuticals effective for musculoskeletal health and cognitive function? A scoping review

ObjectiveThe aim of our scoping review was to summarize the state of the art regarding micronutrients in order to identify which of them might effectively improve health status in the areas typically impaired in older people: bone, skeletal muscle, and cognitive function.DesignScoping review.MethodsThe Italian Study Group on Healthy Aging by Nutraceuticals and Dietary Supplements (HANDS) performed this scoping review, based on the following steps: doing a list of micronutrients related with musculoskeletal or cognitive functions, included in dietary supplements and nutraceuticals commercialized in Italy; planning a research on PubMed, according to an evidence-based approach, in order to the most relevant positive study for each micronutrient into each of the three areas involved (bone, skeletal muscle and cognitive function); identifying the micronutrients effective in maintaining or achieving an adequate health status in older people, specifying the effective and safe daily doses, according to the selected studies.ResultsIn literature we found 12 relevant positive studies (1 international society guidelines/recommendations, 1 systematic review, 7 randomized controlled trials, and 3 prospective cohort studies). We showed that only 16 micronutrients resulted to have appropriate scientific evidences in terms of improving musculoskeletal health and/or cognitive function in older people: beta-alanine, calcium, creatine, fluorides, leucine, magnesium, omega-3 fatty acids, potassium, vitamin B6, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K2, and zinc.ConclusionThis scoping review showed that selected micronutrients in adequate doses might have an ancillary role in musculoskeletal health and cognitive functions in older people.

Can vitamin D deficiency influence muscle performance in post-menopausal women? A multicenter retrospective study.

BACKGROUND The presence of the vitamin D receptor (VDR) has been recently demonstrated in human muscle supporting the theory of a role of vitamin D in the proliferation and differentiation of muscle cells. So far only few studies investigated the association between vitamin D and muscle performance in postmenopausal women. AIM To define the functional impact of vitamin D deficiency. DESIGN Multicenter retrospective study. SETTING Five Italian outpatient services of Physical and Rehabilitation Medicine (PRM). POPULATION Postmenopausal women. METHODS We divided the population in two groups based on the threshold of 30 ng/mL as cut-off to define sufficient and insufficient serum levels of 25-hydroxyvitamin D3 [25(OH)D3]. Outcome measures were: appendicular lean mass (ALM); ALM-to-BMI ratio (ALMBMI); total fat mass (FM); visceral adipose tissue (VAT); Hand Grip Strength (HGS); Knee Isometric Extension Strength (KES); Short Physical Performance Battery (SPPB); 4-meter gait speed (4MGS). RESULTS We analyzed the data records of 401 postmenopausal women (mean age 66.93±8.47 years): 203 with hypovitaminosis D (mean age 66.81±8.11 years) and 198 with normal levels of 25(OH)D3 (mean age 67.04±8.84 years). The analysis showed a significant difference between the two groups in terms of: ALMBMI (0.002), FM (P<0.001), VAT mass (0.010), VAT volume (P=0.006), HGS (P<0.001), KES (P<0.001), SPPB score (P<0.001), percentage of people with a 4MGS≤0.8 m/s (P<0.001). Furthermore, there were significant correlations (P<0.001) between serum levels of 25(OH)D3 and HGS (r=0.323), KES (r=0.510), and SPPB sit to stand (r=-0.362) and walking sub-scores (r=-0.312). CONCLUSIONS This multicenter study demonstrated that postmenopausal women with vitamin D deficiency had a significant reduction of appendicular muscle strength and physical performance. CLINICAL REHABILITATION IMPACT This study reported the frequency of hypovitaminosis D in postmenopausal women and its influence on the reduction of muscle mass, strength, and physical performance in a typical population referring to the physiatrist for musculoskeletal disorders.

Clinical guidelines for the prevention and treatment of osteoporosis: summary statements and recommendations from the Italian Society for Orthopaedics and Traumatology

AbstractBackground The Italian Society for Orthopaedics and Traumatology conceived this guidance—which is primarily addressed to Italian orthopedic surgeons, but should also prove useful to other bone specialists and to general practitioners—in order to improve the diagnosis, prevention, and treatment of osteoporosis and its consequences.Materials and methodsLiterature reviews by a multidisciplinary team.ResultsThe following topics are covered: the role of instrumental, metabolic, and genetic evaluations in the diagnosis of osteoporosis; appraisal of the risk of fracture and thresholds for intervention; general strategies for the prevention and treatment of osteoporosis (primary and secondary prevention); the pharmacologic treatment of osteoporosis; the setting and implementation of fracture liaison services for tertiary prevention. Grade A, B, and C recommendations are provided based on the main levels of evidence (1–3). Toolboxes for everyday clinical practice are provided.ConclusionsThe first up-to-date Italian guidelines for the primary, secondary, and tertiary prevention of osteoporosis and osteoporotic fractures are presented.

Management of atypical femoral fracture: a scoping review and comprehensive algorithm

BackgroundAtypical femoral fractures (AFF) are a rare type of femoral stress fracture recently described, potentially associated with prolonged bisphosphonate therapy. Evidence-based recommendations regarding diagnosis and management of these fractures are scarce. The purpose of this study is to propose an algorithm for the diagnosis and management of AFF.MethodsWe performed a PubMed search of the last ten years using the keywords “atypical femoral fractures” and identified further articles through an evaluation of the publications cited in these articles. Relevant studies were included by agreement between researchers, depending on their specialization. Pertinent points of debate were discussed based on the available literature, allowing for consensus regarding the proposed management algorithm.ResultsUsing a systematic approach we performed a scoping review that included a total of 137 articles.ConclusionsA practical guide for diagnosis and management of AFF based on the current concepts is proposed. In spite of the impressive large volume of published literature available since AFF were initially identified, the level of evidence is mostly poor, in particular regarding treatment choice. Therefore, further studies are required.

Treatment of complex regional pain syndrome

Complex Regional Pain Syndrome (CRPS) is a multifactorial and disabling disorder with complex etiology and pathogenesis. Goals of therapy in CRPS should be pain relief, functional restoration, and psychological stabilization, but early interventions are needed in order to achieve these objectives. Several drugs have been used to reduce pain and to improve functional status in CRPS, despite the lack of scientific evidence supporting their use in this scenario. They include anti-inflammatory drugs, analgesics, anesthetics, anticonvulsants, antidepressants, oral muscle relaxants, corticosteroids, calcitonin, bisphosphonates, calcium channel blockers and topical agents. NSAIDs showed no value in treating CRPS. Glucocorticoids are the only anti-inflammatory drugs for which there is direct clinical trial evidence in early stage of CRPS. Opioids are a reasonable second or third-line treatment option, but tolerance and long term toxicity are unresolved issues. The use of anticonvulsants and tricyclic antidepressants has not been well investigated for pain management in CRPS. During the last years, bisphosphonates have been the mostly studied pharmacologic agents in CRPS treatment and there are good evidence to support their use in this condition. Recently, the efficacy of intravenous (IV) administration of neridronate has been reported in a randomized controlled trial. Significant improvements in VAS score and other indices of pain and quality of life in patients who received four 100 mg IV doses of neridronate versus placebo were reported. These findings were confirmed in the open-extension phase of the study, when patients formerly enrolled in the placebo group received neridronate at the same dosage, and these results were maintained at 1 year follow-up. The current literature concerning sympathetic blocks and sympathectomy techniques lacks evidence of efficacy. Low evidence was recorded for a free radical scavenger, dimethylsulphoxide (DMSO) cream (50%). The same level of efficacy was noted for vitamin C (500 mg per day for 50 days) in prevention of CRPS in patients affected by wrist fracture. In conclusion, the best available therapeutic approach to CRPS is multimodal and is based on the use of several classes of drugs, associated to early physiotherapy. Neridronate at appropriate doses is associated with clinically relevant and persistent benefits in CRPS patients.

NSAIDs and opioids in management of fragility fractures

Fragility fractures and their care are a major burden on individuals, health systems, and social care systems in industrialized countries. Fragility fracture can lead to long lasting painful and disabling condition. The level of pain is a major determinant for the outcome of any treatment of these fractures regardless of its location. The treatment of pain in patient with fragility fracture is rarely considered a priority in the care pathway.

Functional Evaluation of the Subjects with Skeletal Alterations

The appropriate management of osteoporotic patients, with or without fragility fracture, should include a comprehensive functional evaluation in order to define the alterations in functioning of the various organs and systems involved in the pathological process and its complications. The functional evaluation has to follow to an accurate anamnesis and inspection of the patient and should collect information on the range of motion of the joints, on muscle mass, strength, and power, and on balance, disability, and pain. An assessment of the Health Related Quality of Life is also mandatory as its improvement should be the major goal of any treatment.

Rehabilitation of Older Patients with Mental Disorders

The anatomical and histological changes that take place in the ageing brain can significantly impair the cognitive functions of elderly people, such as memory, learning and specific motor functions, affecting their autonomy and quality of life (QoL). Many factors appear to be involved in developing cognitive impairment in older people, including genetics, neuroendocrinology, lifestyle habits and nutrition, as well as social and cultural milieu.

Rehabilitation Therapy After Surgery in Osteoporotic Patients

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fragility fractures that could induce long-term morbidity, functional limitation, decreased quality of life, and increase mortality. The most frequent sites of fragility fractures are the vertebrae, hip, wrist, proximal humerus, and ankle. In several cases, a surgical approach with subsequent rehabilitative treatment is required. The main aims of rehabilitation are restoring pre-fracture functioning and improving patients’ activities, participation level, and quality of life.