Rates and reasons for lack of persistence with anti-osteoporotic drugs: analysis of the Campania region database.

Subjects with chronic diseases are more likely to be nonpersistent to pharmacological treatment. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture. The aim of our retrospective study is to analyze the rates and reasons for discontinuation of anti-osteoporotic drugs in the Campania Region. Subjects aged over 40 years were included if they had received at least one prescription for any anti-osteoporotic drugs. Data were obtained from an administrative database of regional data on outpatient drug prescriptions reimbursed by the National Health Service. Patients were followed until the discontinuation of anti-osteoporotic therapy or until the end of the observation period. A total of 30,048 were incident users of anti-osteoporotic drugs: 28,317 (94.2%) females. The mean age of the cohort was 69.0±10.0 years. Weekly bis-phosphonates (51.1%) were the most commonly prescribed drugs. In the overall population, persistence rates were 34.8% after 6 months and 13.4% at one year. A multivariate Cox proportional hazard analysis showed that daily regimen (HR 1.9) treatments remained at higher risk of early discontinuation compared to weekly regimen therapies. Our data showed that the persistence to osteoporosis therapy is significantly worse than reported in literature.

Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia.

Osteonecrosis is a significant adverse effect of treatment administered to children suffering from acute lymphoblastic leukemia (ALL) that may have a negative effect on the quality of life. The purpose of this study is to evaluate the rate of secondary vascular osteonecrosis (ON) in a population of pediatric patients with ALL treated with corticosteroids and cytostatic agents. A retrospective analysis of prospectively collected data of the medical records of 328 patients with ALL identified 4 cases with ON, corresponding to 1.2% of all cases observed. Of the 4 patients identified in our study 3 were girls and 1 was a boy, aged from 10 to 16 years old (average age at diagnosis, 12 years). Median time between the diagnosis of ALL and ON was 12.5 months (range, 12 to 36 months). Regarding the lesion size of ON, in all cases the femoral head (monolateral in 1 case and bilateral in 3 cases) was involved and was associated with the scapula-humeral joint in one case. ON of the weight-bearing joints has been identified as a severe complication in children with leukemia that may be associated with the development of articular surface collapse, subsequent debilitating arthritis, sometimes needing arthroplasty. For this reason it is very important to implement prevention strategies, especially in adolescent girls treated with steroids and chemotherapy. An early diagnosis of ON and careful orthopedic follow-up are necessary in order to avoid bone deformations related to the late start or the wrong therapy.

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.

Differentiation of human umbilical cord-derived mesenchymal stem cells, WJ-MSCs, into chondrogenic cells in the presence of pulsed electromagnetic fields.

During cartilage regeneration, proliferation and differentiation of new chondrocytes are required and towards this goal, in humans electromagnetic stimulation has been used in order to increase the spontaneous regenerative capacity of bone and cartilage tissue. In vivo tissue engineering has pointed out that the absence of an abundant source of cells accelerating the healing process is a limiting factor in the ability to repair articular cartilage. Considering that the umbilical cord is a viable alternative source of mesenchymal stem cells (MSC), our study evaluated the possibility of a combined use of Wharton's jelly - mesenchymal stem cells (WJ-MSCs) and pulsed electromagnetic field (PMEF). The first effect observed was that compared with the untreated cells, when the WJ-MSCs were treated with PMEF, there was an increase in the division of cells and a rapid increase in cell density and the morphological and biochemical data showed that the treatment with PMEF reduced the time to obtain chondrocyte cell differentiation and deposition of extracellular matrix. Taken together these data indicate the capacity of PEMF to induce early differentiation of WJ-MSCs cells towards cartilaginous tissue.

Musculoskeletal problems in pediatric acute leukemia.

Acute leukemia (AL) in children can mimic several orthopedic pathologies at presentation, with a variable delay in the correct diagnosis. This is a major problem, which may result in fractures, loss of mobility, and deformity, with resultant adverse effects on quality of life. Here, we studied the clinical and radiological musculoskeletal manifestations in children with AL. We reviewed 328 children [208 boys (62%), median age 7.2 years] with acute lymphoblastic (279, 85%) or myeloid (49, 15%) leukemia, treated between January 1982 and December 2003 by the Paediatric Oncology Service, Second University of Naples. The group was further divided into two groups: group 1 included 255 patients (78%, 163 boys) without skeletal morbidity at diagnosis, and group 2 included 73 patients (22%, 41 boys) with musculoskeletal symptoms. This group was further subdivided into group 2A (56 patients), which included children with symptoms related to the appendicular skeleton, and group 2B (17 patients), which included children with symptoms related to the axial skeleton. Moreover, we also reported the long-term complications of therapy, such as osteonecrosis of the weight-bearing joints. In group 2A, 44 children presented only pain, seven septic arthritis-type symptoms, and five osteomyelitis-type symptoms. Joint compression was in the tibia-tarsus (21 patients), knee (16), coxofemoral (12), and elbow (seven). In group 2B, 11 patients presented with vertebral collapses. The remaining six patients complained of localized pain in the lumbar-sacral area, with limited flexor and extensor muscle capacity. Fifty-five (75.3%) patients showed radiographic abnormalities: osteoporosis in 22 patients (40%), pathological fractures in 11 (20%), osteolysis in 10 (18.1%), osteosclerosis in five (9%), periosteal reactions in four (7.2%), and metaphyseal bands in three (5.4%). Four (1.2%) patients in total showed avascular necrosis (4.3% when only high-risk patients were considered). At presentation, 22% of our children had at least one musculoskeletal manifestation and 75.3% showed one radiographic change. Our study highlights the importance of including AL in the differential diagnosis of musculoskeletal manifestations. Four cases of avascular necrosis confirm the need for regular check-ups, both orthopedic and nonorthopedic, particularly in adolescent girls, to prevent permanent disability.

Differentiation of human osteoprogenitor cells increases after treatment with pulsed electromagnetic fields.

Human mesenchymal stem cells (hMSC) have become an important resource in developing strategies for regenerative medicine and tissue engineering, owing to their ability to renew and their potential for differentiation into cells of various types of tissues. Pulsed electromagnetic field (PEMF) stimulation has been used for several years in the treatment of fracture healing, with clinical beneficial effects, and several studies have demonstrated its capacity to increase bone tissue regeneration. In the present study, stromal cells of human bone marrow (BMSC), obtained from healthy donors, were appropriately expanded and underwent PEMF stimulation eight hours a day for fourteen days. Parameters such as proliferation and differentiation ability were evaluated on stimulated cultures. The evaluation of the marker expression was performed by RT-PCR for osteocalcin, by alkaline phosphatase quantitation and by histochemical stains. The results we obtained showed that BMSC treated with PEMF begin differentiation earlier than untreated BMSC, as shown by the markers used. The data show that PEMF is able to increase the osteogenic differentiation potential in adult mesenchymal cells isolated from young patients.

Rehabilitative treatment in flexible flatfoot: a perspective cohort study.

Paediatric valgus flexible flatfoot is a common childhood paramorphism. Its treatment options consist of rehabilitation, corrective footwear and, if necessary, surgical intervention. The aim of our study was to compare a group of children who followed a rehabilitative programme versus a historical group of children who had been treated with insoles and orthopaedic footwear. Over a 2 year period (1995-1997), 300 children (mean age was 3.4-184 male, 116 female) with bilateral flexible flatfoot (600 feet) were recruited and underwent a rehabilitative programme for a mean period of 2.75 years. The feet were classified according to Viladot's method: 386 feet presented a type III degree deformity and 214 feet presented a type II degree deformity. The rehabilitative programme consisted of simple therapeutic exercises, which could be easily learnt by both patients and their caregivers. These children were compared to a historical group of children (674 feet) who had been treated in our department for infantile flexible flatfoot with the use of orthosis. In these groups, 396 feet presented a type III degree deformity and 278 feet presented a type II degree deformity. In the group of children who underwent the rehabilitative protocol, during follow-up at the age of eight, 352 of the 386 type III degree feet could be classified as normal and 210 of the 214 type II degree cases became normal. In the historical cohort of children treated with orthosis, at the age of eight, 214 of the 396 type III degree feet could be classified as normal; and 248 of the 278 type II degree cases became normal. Our results show that comparing the percentage of success (changing from type III or II degree to type I or N) in the two groups (children treated with rehabilitation and children treated with orthosis), the rehabilitative approach seems to be more effective. Probably it has a marginal influence on the natural history of paediatric valgus flexible flatfoot even though it plays a role in maintaining good flexibility of the flatfoot thus limiting functional impairment.

A family with X-linked recessive fusion of metacarpals IV and V.

We describe a family with a distinctive malformation of the hand consisting of the fusion of the 4th and the 5th metacarpal bones. Usually this anomaly is clinically recognizable by an ulnar deviation of the 5th finger; moreover, the 5th metacarpal is usually hypoplastic and the 5th ray is consequently short. There is, however, great variability in expression, so the degree of fusion may range from minimal to complete and also the external aspect of the hand may vary. This anomaly can be either isolated or part of a syndrome. For the isolated form, two possible hereditary mechanisms have been proposed: autosomal dominant and X-linked recessive. Our family is consistent with the latter, with only affected males and no instances of male-to-male transmission. Of note, there are very few X-linked recessive disorders that affect the hand in a such a specific way.