Elena Gasbarra

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.

Sarcopenia and fragility fractures: molecular and clinical evidence of the bone-muscle interaction

➤ Bone and muscle tissues are in close relationship, and the aging process is a factor involved in the loss of the functionality of both bones and muscles.➤ Sarcopenia and osteoporosis are linked from a biological and functional perspective and are related to an increased fracture risk in the elderly.➤ The increased fracture risk in sarcopenic and osteoporotic subjects is due to the decline of muscle mass and strength, the decrease in bone mineral density, and limited mobility.

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.

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.

Fragility fractures: the clinical pathway

The clinical management of fragility fracture is simple but complex at the same time. Patients are different from one another, and advancing age increases the prevalence of comorbidities and conditions that can impair bone quality and healing, while increasing the risk of falls and fractures. Keeping in mind some principles and key points can help identify patients at risk, thus following an ideal path for the identification, treatment and prevention of fragility fractures.

Low FT3: a possible marker of frailty in the elderly

Introduction Frailty is associated with a functional decline of multiple physiological systems, of which they may be a cause or consequence. The objective of the study was to evaluate the prevalence of thyroid hormone modifications in elderly frail subjects and its relationship with frailty. Study population and methods An observational study was carried out at the University Hospital “Tor Vergata” in Rome among ambulatory and hospitalized patients. The study population consisted of 112 elderly subjects: 62 were hospitalized following hip fracture and 50 control subjects were outpatients. Participating patients received a multidimensional geriatric evaluation. The Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI) was used to assess the degree of frailty. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured to evaluate thyroid status. Results FT3, but not FT4, was significantly correlated with Frailty score, both in patients with hip fracture and in patients from the control group. In the entire study population, FT3 under normal limits is effective in discriminating frail/prefrail subjects from nonfrail subjects. Discussion The reduction in serum concentrations of FT3 is a clear manifestation of stress associated with fractures. Numerous preexisting factors, such as the fracture patients’ nutritional status, sarcopenia, disability and comorbidities, which characterize the condition of frailty and influence its pathogenesis, are strongly correlated with FT3 values, suggesting the existence of latent nonthyroidal illness syndrome (NTIS). Conclusion We conclude that measuring FT3 can be a useful laboratory parameter in clinical assessment, which can play an important role in identifying vulnerable elderly subjects and in quantifying the condition of frailty.

Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed by in situ molecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology.

Hip fractures in the elderly: the role of cortical bone

INTRODUCTION Osteoporosis is characterised by poor bone quality arising from alterations to trabecular bone. However, recent studies have also described an important role of alterations to cortical bone in the physiopathology of osteoporosis. Although dual-energy X-ray absorptiometry (DXA) is a valid method to assess bone mineral density (BMD), real bone fragility in the presence of comorbidities cannot be evaluated with this method. The aim of this study was to evaluate if cortical thickness could be a good parameter to detect bone fragility in patients with hip fracture, independent of BMD. METHODS A retrospective study was conducted on 100 patients with hip fragility fractures. Cortical index was calculated on fractured femur (femoral cortical index [FCI]) and, when possible, on proximal humerus (humeral cortical index [HCI]). All patients underwent densitometric evaluation by DXA. RESULTS Average value of FCI was 0.43 and of HCI was 0.25. Low values of FCI were found in 21 patients with normal or osteopenic values of BMD, while low values of HCI were found in three patients with non-osteoporotic values of BMD. DISCUSSION AND CONCLUSION Cortical thinning measured from X-Ray of the femur identifies 21% additional fracture cases over that identified by a T-score <-2.5 (57%). FCI could be a useful tool to evaluate bone fragility and to predict fracture risk even in patients with normal and osteopenic BMD.

Role of Metalloproteinases in Tendon Pathophysiology

Tendons play a crucial role in musculoskeletal functioning because they physically connect bones and muscles making the movement of articular joints possible. The molecular composition of tendons mostly include collagen I fibrils, which aggregate together to form fibers to form a fascicle. A complex network composed of resident cells (i.e., tenocytes) and extracellular matrix macromolecules (glycosaminoglycans, proteoglycans, glycoproteins and other non collagenous proteins) interact and define the structure of tendons and their properties. Development, renewal and remodeling of tendons composition occur at all ages of living organisms so the homeostasis of proteolytic systems is a critical issue. A major role is played by Metalloproteinases, a family of Zn(2+)-dependent endopeptidases involved in the catabolism of several components of the extracellular matrix, such as collagens, proteoglycans, fibronectin and many others. Among these, two main classes are mostly involved in tendon pathophysiology, namely the Matrix Metalloproteinases (MMPs) and a Disintegrin-like and Metalloproteinase domain with Thrombospondin motifs (ADAMTSs). This study analyses the various aspects of the roles played by Metalloproteinases in the physiological and pathological processes of tendons.