Monica Celi

Osteoporosis and sarcopenia: the connections

Osteoporosis and sarcopenia are the most frequent musculoskeletal disorders affecting older people. Osteoporosis is a widespread disorder affecting millions of individuals of all ethnic backgrounds worldwide, particularly among older women. It is characterized by reduced bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in the risk of fracture. Sarcopenia is considered to be one of the major factors responsible for functional limitations and motor dependency in elderly persons. In age-related muscle atrophy, a decrease in muscle fiber size and number, and a preferential loss of type II fibers have been reported. A decrease in the circulating levels of specific hormones (e.g., estrogen, testosterone, growth hormone, and insulin-like growth factor-1) has been shown to be associated with sarcopenia and this appears to play an important role in its pathogenesis.

Long-term effect of exercise on bone mineral density and body composition in post-menopausal ex-elite athletes: a retrospective study.

Objectives:The aim of this retrospective study was to determine the long-term effect of exercise on bone mineral density (BMD), bone mineral content (BMC) and body composition (BC) in post-menopausal women who were elite athletes during their youth compared with sedentary controls.Subjects/Methods:It is a retrospective study and carried out in an outpatient clinic. A total of 48 post-menopausal women (54–73 years of age) were enrolled. Ex-elite athletes with long-term (>20 years) histories of significant training and performance were divided into two groups: weight-bearing sports (runners, n=12) and non-weight-bearing sports (swimmers, n=12). The athletes were age matched with sedentary controls (n=24). BMD, BMC and BC were measured using dual-energy X-ray absorptiometry. Healthcare and sport activity histories were evaluated using a questionnaire.Results:No significant differences were found with regard to body weight, height, body mass index and hours of activity between the two groups of athletes. There were no significant differences in activity levels between athletes and controls at the time of this study. BMD and BMC were not significantly different between athletes; they were significantly higher in athletes than in controls (P<0.001). Although the ex-athletes did not significantly differ in BC, left and right lean arm mass and arm BMD were significantly higher in swimmers than in runners (P<0.0001).Conclusions:The high level of physical activity observed in female athletes is associated with improved muscle mass, BMD and BMC, and physical activity during youth seems to have a beneficial effect on bone mass and helps to prevent bone loss due to aging.

Transglutaminases expression in human supraspinatus tendon ruptures and in mouse tendons.

The ethiopathogenesis of rotator cuff disease remains poorly understood. Many studies advocate the importance of extra cellular matrix for the homeostasis of connective tissue. Transglutaminase enzymes family has been studied in the context of connective tissue formation and stabilisation. Here, we investigated transglutaminases expression pattern in biopsies of normal and injured supraspinatus tendons of human shoulders and in the Achilles tendons of transglutaminase 2 knock-out and wild-type mice. Our results show that different transglutaminase family members are differentially expressed in human and mouse tendons, and that transglutaminase 2 is down-regulated at mRNA and protein levels upon human supraspinatus tendon ruptures.

Ten years of hip fractures in Italy: For the first time a decreasing trend in elderly women

AIM To evaluate the hospitalization rate of femoral neck fractures in the elderly Italian population over ten years. METHODS We analyzed national hospitalizations records collected at central level by the Ministry of Health from 2000 to 2009. Age- and sex-specific rates of fractures occurred at femoral neck in people ≥ 65 years old. We performed a sub-analysis over a three-year period (2007-2009), presenting data per five-year age groups, in order to evaluate the incidence of the hip fracture in the oldest population. RESULTS We estimated a total of 839008 hospitalizations due to femoral neck fractures between 2000 and 2009 in people ≥ 65, with an overall increase of 29.8% over 10 years. The incidence per 10000 inhabitants remarkably increased in people ≥ 75, passing from 158.5 to 166.8 (+5.2%) and from 72.6 to 77.5 (+6.8%) over the ten-year period in women and men, respectively. The oldest age group (people > 85 years old) accounted for more than 42% of total hospital admissions in 2009 (n = 39000), despite representing only 2.5% of the Italian population. Particularly, women aged > 85 accounted for 30.8% of total fractures, although they represented just 1.8% of the general population. The results of this analysis indicate that the incidence of hip fractures progressively increased from 2000 to 2009, but a reduction can be observed for the first time in women ≤ 75 (-7.9% between 2004 and 2009). CONCLUSION Incidence of hip fractures in Italy are continuously increasing, although women aged 65-74 years old started showing a decreasing trend.

Bone mineral density evaluation in osteoporosis: why yes and why not?

Osteoporosis is a diffuse skeletal disease in which a decrease in bone strength leads to an increased risk of fractures. A wide variety of types of bone densitometry measurements are available, including quantitative computed tomography measurements of the spine, quantitative ultrasound devices for measurements of the heel and other peripheral sites and dual-energy X-ray absorptiometry (DXA) for measurement of bone mineral density (BMD) at the lumbar spine, proximal femur, forearm and total body scans. Compared with alternative bone densitometry techniques, hip and spine DXA examinations have a number of advantages that include a consensus that BMD results can be interpreted using the World Health Organization T score definition of osteoporosis, a proven ability to predict fracture risk, proven effectiveness at targeting anti-fracture therapies, and the ability to monitor response to treatment. However, in recent years, the authors have raised some important questions about the objective limits of this method that have led to doubts about its effectiveness in terms of clinical outcome.

Open medial dislocation of the ankle without fracture

A 20-year-old man sustained an open medial dislocation of the ankle without an associated fracture after a low-energy inversion injury. Prompt debridement and reduction with primary wound closure of the skin were performed without suture of the capsule. Immobilisation in a non-weight-bearing cast for 30 days followed by ankle bracing for two weeks and subsequent physiotherapy, produced full functional recovery by three months. At follow-up at one year there was a full range of pain-free movement, although the radiographs and MR scan showed early post-traumatic degenerative change at the medial aspect of the tibiotalar and the calcaneocuboid joints.

Hip osteoarthritis and osteoporosis: clinical and histomorphometric considerations.

Although an inverse relationship between osteoarthritis (OA) and osteoporosis (OP) has been shown by some studies, other reports supported their coexistence. To clarify this relationship, we analyzed the interplay between clinical and histomorphometric features. Bone mineral density (BMD) and histomorphometric structure were assessed in 80 patients of four different age-matched groups undergoing hip arthroplasty for severe OA or OP-related femoral fracture. Harris Hip Score was also performed. Surgical double osteotomy of the femoral head was performed and microscopic bone slice samples analysis was performed by using a BioQuant Osteo software. Bone volume fraction (BV/TV) was lower (P < 0.01) in subjects with femoral neck fracture (20.77 ± 4.34%) than in subjects with nonosteopenic OA (36.49 ± 7.73%) or osteopenic OA (32.93 ± 6.83%), whereas no difference was detected between subjects with femoral neck fractures and those with combined OA and OP (20.71 ± 5.23%). Worse Harris Hip Score was found in those patients with the lowest BMD and BV/TV values. Our data support recent evidences indicating the possibility of impaired bone volume fraction in OA patients, with a high risk of developing OP, likely for their decreased mobility. Further studies are needed in order to investigate biomolecular pathway and/or growth factors involved in bone volume impairment in OA patients.

Osteoblasts display different responsiveness to TRAIL-induced apoptosis during their differentiation process.

Apoptosis can occur throughout the life span of osteoblasts (OBs), beginning from the early stages of differentiation and continuing throughout all stages of their working life. Here, we investigated the effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal human OBs showing for the first time that the expression of TRAIL receptors is modulated during OB differentiation. In particular, the TRAIL receptor ratio was in favor of the deaths because of the low expression of DcR2 in undifferentiated OBs, differently it was shifted toward the decoys in differentiated ones. Undifferentiated OBs treated with TRAIL showed reduced cell viability, whereas differentiated OBs displayed TRAIL resistance. The OB sensitiveness to TRAIL was due to the up-regulation of DR5 and the down-regulation of DcR2. The main death receptor involved in TRAIL-reduced OB viability was DR5 as demonstrated by the rescue of cell viability observed in the presence of anti-DR5 neutralizing antibody. Besides the ratio of TRAIL receptors, the sensitivity of undifferentiated OBs to TRAIL-cytotoxic effect was also associated with low mRNA levels of intracellular anti-apoptotic proteins, such as cFLIP, the activation of caspase-8 and -3, as well as the DNA fragmentation. This study suggests that apoptotic effect exerted by TRAIL/TRAIL-receptor system on normal human OB is strictly dependent upon cell differentiation status.

The bone anabolic therapy

Teriparatide (TPTD), the amino-terminal parathyroid hormone recombinant peptide [PTH (1–34)], is a drug with a proven anabolic action on the bone, effective in preventing vertebral and non-vertebral fragility fractures. Recent publications have investigated in great detail the TPTD action on the cortical bone, highlighting the increased strength in the critical zone of the hip with high risk of fracture in osteoporotic patients Poole (PLoS ONE 6:e16190, 2011). In November 2002, TPTD was approved by the FDA for use in post-menopausal women and men with osteoporosis at high risk of fracture and in patients with glucocorticoid-induced osteoporosis and, since then, has been used to treat more than 1 million patients worldwide (J Bone Miner Res 27(12):2429–2437, 2012). The unchanged safety profile and the well-known mechanism of action of this drug have led doctors to explore the use of TPTD in other conditions such as delayed fracture healing, non-union, osteonecrosis of the jaw, etc. The positive reports that have resulted from these studies are helping to hypothesize a new perspective on the wider use of this drug, but warrant further clinical investigation to consolidate these results.

Evaluation of persistence and adherence to teriparatide treatment in patients affected by severe osteoporosis (PATT): a multicenter observational real life study.

INTRODUCTION Osteoporosis is a chronic condition leading to an increased risk of developing fractures, with high morbidity and mortality in aging population. Efficacy of anti-osteoporotic treatment is based on drug potency but also on compliance and persistence to treatment regimen, which is very low, as already described for other diseases. Teriparatide (TPTD) is the first anabolic agent developed for the treatment of osteoporosis. Since it appears that persistence to Teriparatide declines over time, aim of this pilot multicenter observational study was to evaluate persistence and adherence to TPTD (20 μg daily injection regimen for 18 months) treatment (PATT) in patients affected by severe osteoporosis in an every day clinical practice. METHODS Patients affected by severe osteoporosis were selected among those who referred to 5 different specialized centers for osteoporosis in North, Center and South of Italy. A sample of 475 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the Italian osteoporosis guidelines was included. At the beginning of TPTD treatment patients were instructed on the use of the device by the referring specialist of the center, a resident fellow or a nurse. Bone biochemical markers were evaluated the same morning and after 1, 3, 6, 12 and 18 months. Patients were visited at time 0 and after 6, 12 and 18 months for clinical follow up. RESULTS The results included observations of 441/475 patients (98% women) who completed the 18 months treatment; mean age for women was 73±8 and for men 65±9. After 6 months of TPTD treatment persistence was of 89,79%, 87,75% after 12 months and 86,85% after 18 months. Adherence was of 100% at 6,12 and 18 months. Total dropouts were 13,15% (71/441), which was usually higher within the first 6 months of TPTD treatment. Most common adverse events (arthralgies 2,7%, dizziness 1,8%, migraine 1,8%, depression 1,6%, hypertension 1,1%) were reported in 62/441 patients (14%) of patients, but were not reason for stopping treatment. CONCLUSIONS The persistence and adherence to TPTD treatment obtained in this multicenter observational real life study was very high as compared to studies performed by others. These encouraging results suggest that different key factors such quality of information, frequency of visits, motivations given to patients, opportunity to call the doctor might play a pivotal role in the high persistence and adherence to TPTD treatment obtained in our study and need to be carefully considered before prescribing chronic anti-osteoporotic therapy.