Use of teriparatide off-label: our experience and review of literature.

The aim of this paper is to report our experience and to present a review of literature about the use of teriparatide off-label in the therapy of non-unions. Teriparatide is used exclusively in treatment of osteoporosis and to prevent bone fracture because it has a positive effect on bone strength and architecture. The use of teriparatide in non-unions is described as effective in numerous case report.

Efficacy of teriparatide vs neridronate in adults with osteogenesis imperfecta type I: a prospective randomized international clinical study.

Osteogenesis imperfecta (OI) is an hereditary disease characterized by low bone mass, increased bone fragility, short stature, and skeletal deformities, few treatment options are currently available. Neridronate is an amino-bisphosphonate, licensed in Italy for the treatment of OI and Paget's disease of bone. A characteristic property of neridronate is that it can be administered both intravenously and intramuscularly, providing an useful system for administration in homecare. Neridronate appears to increase Bone Mineral Density (BMD) in adults with OI and reduces bone resorption by inhibition of osteoclastic activity. Teriparatide (recombinant 1-34 N terminal sequence of human parathyroid hormone) is the first anabolic agent approved for the treatment of patients with osteoporosis and has been reported to increase bone formation by stimulating osteoblast differentiation, osteoblast function, and survival. The results of this study showed a promising role of teriparatide in the therapy of OI type I.

The role of drugs in bone pain.

Painful symptomatology in the skeletal system can be found in various pathological conditions and can be either localised or diffused. Bone tenderness is common in those who are of an elderly age. TREATMENT STRATEGY: Patients should be informed of the possible causes of their pain and the different therapies that could alleviate it; furthermore they should be encouraged to have an active role in their therapy. It is necessary to prevent the onset of the pain (by the clock) by considering the biological half-life, the bioavailability and the duration of action of the therapy. According to the World Health Organization (WHO), pain treatment is based on a three-step ladder. ADJUVANT THERAPIES: Adjuvant therapies are often associated with the drugs in the WHO three step ladder. This heterogeneous group of non-analgesic drugs is used in the treatment of bone pain by bettering the analgesia or reducing the side effects brought on by analgesics. CONCLUSION: In the daily struggle that doctors face to treat their patients, pain management should not be disregarded. Among the various types of pain, bone pain, must not be underestimated but be fought against by using all means available. Patients need to be treated depending on the severity of their pain, NSAIDs should be the preferred choice of treatment for acute pain but not for that of chronic pain. In the case of chronic pain opioids should be used in their most recent fomulations as they can guarantee fewer side effects. Patients should also be prescribed adjuvant drugs as well as being given psychological support in order to ensure successful treatment.

Safety and efficacy of vertebroplasty in the treatment of osteoporotic vertebral compression fractures: a prospective multicenter international randomized controlled study.

BACKGROUND: Vertebral compression fractures (VCFs) treated non-operatively can diminish function and quality of life, and lead to chronic health effects. The short-term safety and effectiveness of vertebroplasty for symptomatic VCFs are well-documented, but long-term follow-up is needed. PURPOSE: The aim of this paper was to analyse a multicenter international experience of 200 compression fractures treated with percutaneous vertebroplasty (VP) and compare the results of this procedure with the result of 200 patients treated conservatively. To estimate cost-effectiveness of VP compared to conservative care in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. MATERIALS AND METHODS: 400 patients have been enrolled in a prospective randomized controlled study with painful VCFs with bone edema on MR imaging, local back pain for 6 weeks or less, osteoporosis and aged 55 years or older; after obtaining informed consent patients are included and randomized for VP or conservative care. Before treatment and at follow-up with regular intervals during 1-year period were administered to patients standard questionnaires addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score for pain, Oswestry Disability Index (ODI) score to evaluate functional activity. RESULTS: 200 patients treated with PV compared with 200 patients treated conservatively had significantly better VAS and used less analgesics 1 day after treatment. Twenty-four hours after VP, there was a reduction in pain scores and an improvement in physical functions, whereas remain unchanged in the patients treated conservatively. CONCLUSIONS: Pain relief and improvement of mobility and function after PV is immediate and significantly better in the short term compared with non-surgical care treatment.

Safety and effectiveness of teriparatide vs alendronate in postmenopausal osteoporosis: a prospective non randomized clinical study.

In this work we study the safety and effectiveness of teriparatide and alendronate in patients with postmenopausal osteoporosis at high risk of fracture; it was a double-blinded and it was done by examining the comparisons between teriparatide 20 µg/day and alendronate 10 mg/day. Safety and effectiveness analyses were based on data from 355 woman with a mean age of 68 years. Two groups (A and B) with T-score ≤-2.5 at bone mineral density were analyzed and 3 or more vertebral fractures on radiograph. Group A: was treated with teriparatide 20 µg/day and composed from 182 women, in post-menopausal age, without a history of cancer. Group B: was treated with alendronate 10 mg/day composed from 173 women, postmenopausal age, with previous history of cancer (non-active during the study). Clinical evaluations were on bone turnover markers (alkaline phosphatase, procollagene type 1 N-terminal propeptide, and N-telopeptide cross-links), dual-energy X-ray absorptiometry and health-related quality of life (HrQoL). Safety was assessed by reporting of adverse drug reactions (ADRs). The results of this study imply that teriparatide comparated with alendronate has a favorable safety profile and is effective in the treatment of patients with osteoporosis at high risk of fracture.

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study.

INTRODUCTION: Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. PURPOSE: This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). PATIENTS AND METHODS: In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <-1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for health-related quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs -1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. CONCLUSION: In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Painful prosthesis: approaching the patient with persistent pain following total hip and knee arthroplasty.

BACKGROUND: Symptomatic severe osteoarthritis and hip osteoporotic fractures are the main conditions requiring total hip arthroplasty (THA), whereas total knee arthroplasty (TKA) is mainly performed for pain, disability or deformity due to osteoarthritis. After surgery, some patients suffer from "painful prosthesis", which currently represents a clinical problem. METHODS: A systematic review of scientific literature has been performed. A panel of experts has examined the issue of persistent pain following total hip or knee arthroplasty, in order to characterize etiopathological mechanisms and define how to cope with this condition. RESULTS: Four major categories (non infective, septic, other and idiopathic causes) have been identified as possible origin of persistent pain after total joint arthroplasty (TJA). Time to surgery, pain level and function impairment before surgical intervention, mechanical stress following prosthesis implant, osseointegration deficiency, and post-traumatic or allergic inflammatory response are all factors playing an important role in causing persistent pain after joint arthroplasty. Diagnosis of persistent pain should be made in case of post-operative pain (self-reported as VAS ≥3) persisting for at least 4 months after surgery, or new onset of pain (VAS ≥3) after the first 4 months, lasting ≥2 months. Acute pain reported as VAS score ≥7 in patients who underwent TJA should be always immediately investigated. CONCLUSIONS: The cause of pain needs always to be indentified and removed whenever possible. Implant revision is indicated only when septic or aseptic loosening is diagnosed. Current evidence has shown that peri-and/or post-operative administration of bisphosphonates may have a role in pain management and periprosthetic bone loss prevention.

Dance therapy improves motor and cognitive functions in patients with Parkinson's disease.

OBJECTIVE: To explore the effects of Dance Therapy (DT) and Traditional Rehabilitation (TR) on both motor and cognitive domains in Parkinson's Disease patients (PD) with postural instability. METHODS: Sixteen PD patients with recent history of falls were divided in two groups (Dance Therapy, DT and Traditional Rehabilitation, TR); nine patients received 1-hour DT classes twice per week, completing 20 lessons within 10 weeks; seven patients received a similar cycle of 20 group sessions of 60 minutes TR. Motor (Berg Balance Scale - BBS, Gait Dynamic Index - GDI, Timed Up and Go Test - TUG, 4 Square-Step Test - 4SST, 6-Minute Walking Test - 6MWT) and cognitive measures (Frontal Assessment Battery - FAB, Trail Making Test A & B - TMT A&B, Stroop Test) were tested at baseline, after the treatment completion and after 8-week follow-up. RESULTS: In the DT group, but not in the TR group, motor and cognitive outcomes significantly improved after treatment and retained after follow-up. Significant changes were found for 6MWT (p = 0.028), TUG (p = 0.007), TMT-A (p = 0.014) and TMT-B (p = 0.036). CONCLUSIONS: DT is an unconventional physical therapy for PD patients which effectively impacts on motor (endurance and risk of falls) and non-motor functions (executive functions).

Skeletal fragility definition.

Strategies to reduce fracture risk must be based on the understanding of the mechanisms that underline the increased incidence of fractures with age and with bone diseases that reduce bone stock. There is evidence that in addition to bone minerals density, other factors influence bone strength. This study reviews the biomechanical aspects of age-related fractures, including the interacting roles of traumatic loading and bone strength, and the factors that determine the resistances of bones to fracture. Although low bone mineral density (BMD) is among the strongest risk factors for fracture, a number of clinical studies have demonstrated the limitations of bone mineral density measurements in assessing fracture risk and monitoring the response to therapy. These observations have brought renewed attention to the broader array of factors that influence skeletal fragility, including bone size, shape, micro-architecture and bone quality. Bone fragility can be defined by biomechanical parameters, including ultimate force, ultimate displacement and energy absorption. Many osteoporosis treatments build bone mass but also change tissue quality. Antiresorptive therapies, such as bisphosphonates, substantially reduce bone turnover, impairing micro-damage repair and causing increased bone mineralization, which can increase the brittleness of bone. Anabolic therapies, such as teriparatide, increase bone turnover and porosity, which offset some of the positive effects on bone strength. Osteoporosis therapies may also affect bone architecture by causing the redistribution of bone structure. Restructuring of bone during treatment may change bone fragility, even in the absence of drug effects on BMD.