In Vivo Assessment of Cortical Bone Fragility.

PURPOSE OF REVIEW: This review updates readers on recent developments in the assessment of cortical bone fragility in vivo. The review explains the clinical need that motivated the development of Cortical Bone Mechanics Technology™ (CBMT) as a scientific instrument, its unique capabilities, and its necessary further development as a medical device. RECENT FINDINGS: Clinical experience with dual-energy X-ray absorptiometry has led to calls for new clinical methods for assessing bone health. CBMT is a noninvasive, dynamic 3-point bending test that makes direct, functional measurements of the mechanical properties of cortical bone in ulnas of living people. Its technical validity in accurate measurements of ulna flexural rigidity and its clinical validity in accurate estimations of quasistatic ulna bending strength have been demonstrated. Because CBMT is a whole bone test, its measurements reflect the influences of bone quantity and bone quality at all hierarchical levels.

Improvements to mechanical response tissue analysis.

Cortical Bone Mechanics Technology™ (CBMT) comprises certain improvements over a previous method known as Mechanical Response Tissue Analysis (MRTA). Both methods are dynamic 3-point bending tests intended for measuring the mechanical properties of cortical bone in living people. MRTA presented a theoretical potential for direct measurement of skeletal fragility, but it had acquired a reputation for error and fallen into disuse. We found sources of error in both MRTA data collection and data analysis. We describe here the fundamentals of MRTA, the major sources of error we found in MRTA, and our innovations for avoiding them. •Data collection at many sites across the mid-shaft of the ulna bone in the forearm.•Parameter estimation by fitting analytical complex compliance and stiffness transfer functions to empirical complex compliance and stiffness frequency response functions.•Optimization by selecting results from frequency response functions with the smallest deviations between fits to compliance and stiffness frequency response functions.

A new noninvasive mechanical bending test accurately predicts ulna bending strength in cadaveric human arms.

BACKGROUND: High error rates in the prediction of fragility fractures by bone mineral density have motivated searches for better clinical indicators of bone strength, and the high incidence of non-hip, non-spine fractures has raised interest in cortical bone. The aim of this study was to assess the accuracy of Cortical Bone Mechanics Technology™. CBMT is a new non-invasive 3-point bending technique for measuring the mechanical properties of cortical bone in the ulnas of living humans. METHODS: 35 cadaveric human arms were obtained from small women and large men ranging widely in age (17 < Age < 99 years) and body size (14 < BMI < 40 kg/m2). Noninvasive CBMT measurements of the flexural rigidity of the ulna bones within these arms (EICBMT) were compared to measurements of EI by Quasistatic Mechanical Testing in the ulnas excised from those arms (EIQMT). Ulna bending strength was also measured by QMT as the peak moment before fracture (Mpeak). The open source BoneJ plugin to ImageJ image processing software was used to calculate cortical porosity (CP) in micro-computed tomography images of a 2 mm length of the mid-shaft of each fractured ulna, and the interosseous diameter (IOD) of each ulna was also measured in those images. RESULTS: EICBMT measurements (13 < EICBMT < 97 Nm2) explained 99% of the variance in QMT measurements of ulna bending strength (11 < Mpeak < 90 Nm), but EICBMT was biased high by 30% (p < 0.0001) relative to EIQMT (11 < EIQMT < 69 Nm2). After correcting this bias, EICBMT and EIQMT measurements lay along the identity line (y = 1.00x, R2 = 0.99, SEE = 3.1 Nm2). Predictions of Mpeak by EICBMT were less accurate than predictions by EIQMT (both R2 = 0.99; SEECBMT = 5.9 Nm vs SEEQMT = 4.5 Nm, F = 2.92, p = 0.001), but EICBMT predictions were substantially more accurate than those by IOD (R2 = 0.79; SEEIOD = 10.6 Nm, F = 3.30, p < 0.001) and CP (R2 = 0.35; SEECP = 18.9 Nm, F = 10.45, p < 10-9). Predictions by EICBMT were also more accurate than predictions by arm donor height (R2 = 0.63; SEE = 14.3 Nm, F = 5.87, p < 10-6), body weight (R2 = 0.77; SEE = 11.1 Nm, F = 3.54, p < 0.001) and BMI (R2 = 0.64; SEE = 14.1 Nm, F = 2.39, p < 0.01). In forward stepwise multiple regression beginning with EICBMT, only age explained any additional variance in ulna bending strength (ΔR2 = 0.3%, F = 8.03, p = 0.008). CONCLUSION: Noninvasive CBMT measurements of ulna EI explain 99% of individual differences in QMT measurements of ulna bending strength in cadaveric human arms.

Response to "Clinical Evaluation of Bone Strength and Fracture Risk".

We read with great interest the recent review by de Bakker et al that summarized the state of several existing and emerging technologies for estimating bone strength and fracture risk in vivo. Much of their review focused on how well the measurements of selected technologies predicted experimental measurements of bone strength by ex vivo quasistatic mechanical testing (QMT) and on how well they tracked changes in mechanical properties of bone. The authors noted that the association of many common skeletal health measurements (e.g., DXA measures of trabecular bone score and areal and volumetric BMD) are only moderately associated with bone strength. The authors did not include mechanical response tissue analysis (MRTA) in their review. MRTA is a dynamic mechanical bending test that uses a vibration analysis technique to make immediate, direct, functional measurements of the mechanical properties (mass, stiffness, and damping) of long bones in humans in vivo. In this article we note our interest in the ability of MRTA to detect large changes in bone stiffness that go undetected by DXA. We also highlight results of our proprietary improvements to MRTA technology that have resulted in unmatched accuracy in QMT-validated measurements of the bending stiffness and estimates of the bending strength (both R2 = 0.99) of human ulna bones. To distinguish our improved technique from the legacy MRTA technology, we refer to it as Cortical Bone Mechanics Technology (CBMT). Further research will determine whether such CBMT measurements are clinically useful.

The effects of testosterone and insulin-like growth factor 1 on motor system form and function.

In this perspective article, we review the effects of selected anabolic hormones on the motoric system and speculate on the role these hormones may have on influencing muscle and physical function via their impact on the nervous system. Both muscle strength and anabolic hormone levels decline around middle age into old age over a similar time period, and several animal and human studies indicate that exogenously increasing anabolic hormones (e.g., testosterone and insulin-like growth factor-1 (IGF-1)) in aged subjects is positively associated with improved muscle strength. While most studies in humans have focused on the effects of anabolic hormones on muscle growth, few have considered the impact these hormones have on the motoric system. However, data from animals demonstrate that administering either testosterone or IGF-1 to cells of the central and peripheral motor system can increase cell excitability, attenuate atrophic changes, and improve regenerative capacity of motor neurons. While these studies do not directly indicate that changes in anabolic hormones contribute to reduced human performance in the elderly (e.g., muscle weakness and physical limitations), they do suggest that additional research is warranted along these lines.

Accuracy and reproducibility of bending stiffness measurements by mechanical response tissue analysis in artificial human ulnas.

Osteoporosis is characterized by reduced bone strength, but no FDA-approved medical device measures bone strength. Bone strength is strongly associated with bone stiffness, but no FDA-approved medical device measures bone stiffness either. Mechanical Response Tissue Analysis (MRTA) is a non-significant risk, non-invasive, radiation-free, vibration analysis technique for making immediate, direct functional measurements of the bending stiffness of long bones in humans in vivo. MRTA has been used for research purposes for more than 20 years, but little has been published about its accuracy. To begin to investigate its accuracy, we compared MRTA measurements of bending stiffness in 39 artificial human ulna bones to measurements made by Quasistatic Mechanical Testing (QMT). In the process, we also quantified the reproducibility (i.e., precision and repeatability) of both methods. MRTA precision (1.0±1.0%) and repeatability (3.1 ± 3.1%) were not as high as those of QMT (0.2 ± 0.2% and 1.3+1.7%, respectively; both p<10(-4)). The relationship between MRTA and QMT measurements of ulna bending stiffness was indistinguishable from the identity line (p=0.44) and paired measurements by the two methods agreed within a 95% confidence interval of ± 5%. If such accuracy can be achieved on real human ulnas in situ, and if the ulna is representative of the appendicular skeleton, MRTA may prove clinically useful.

2014 female athlete triad coalition consensus statement on treatment and return to play of the female athlete triad.

The female athlete triad is a medical condition often observed in physically active girls and women and involves three components: (1) low energy availability with or without disordered eating, (2) menstrual dysfunction, and (3) low bone mineral density. Female athletes often present with one or more of the three triad components, and early intervention is essential to prevent its progression to serious end points that include clinical eating disorders, amenorrhea, and osteoporosis. This consensus statement presents a set of recommendations developed following the first (San Francisco, CA) and second (Indianapolis, IN) International Symposia on the Female Athlete Triad. This consensus statement was intended to provide clinical guidelines for physicians, athletic trainers, and other health care providers for the screening, diagnosis, and treatment of the female athlete triad and to provide clear recommendations for return to play. The expert panel has proposed a risk stratification point system that takes into account magnitude of risk to assist the physician in decision making regarding sport participation, clearance, and return to play. Guidelines are offered for clearance categories, management by a multidisciplinary team, and implementation of treatment contracts.

Energy availability in athletes.

This review updates and complements the review of energy balance and body composition in the Proceedings of the 2003 IOC Consensus Conference on Sports Nutrition. It argues that the concept of energy availability is more useful than the concept of energy balance for managing the diets of athletes. It then summarizes recent reports of the existence, aetiologies, and clinical consequences of low energy availability in athletes. This is followed by a review of recent research on the failure of appetite to increase ad libitum energy intake in compensation for exercise energy expenditure. The review closes by summarizing the implications of this research for managing the diets of athletes.

The female athlete triad: components, nutrition issues, and health consequences.

This paper, which was part of the International Association of Athletics Federations (IAAF) 2007 Nutritional Consensus Conference, briefly reviews the components of the female athlete triad (Triad): energy availability, menstrual status, and bone health. Each component of the Triad spans a continuum from health to disease, and female athletes can have symptoms related to each component of the Triad to different degrees. Low energy availability is the primary factor that impairs menstrual dysfunction and bone health in the Triad. We discuss nutritional issues associated with the Triad, focusing on intakes of macronutrients needed for good health, and stress fractures, the most common injury associated with the Triad. Finally, we briefly discuss screening and treatment for the Triad and the occurrence of the Triad in men.

Energy availability and infertility.

PURPOSE OF REVIEW: To relate recent research on the dependence of reproductive function on energy availability in women to recent clinical experience in the treatment of anorexia nervosa. RECENT FINDINGS: The dependence of luteinizing hormone pulsatility on energy availability declines during adolescence, but the responses of leptin and other peripheral signals of energy deficiency do not. This finding suggests that central sensitivity to these signals may decline during adolescence. Energy availability may be inadequate in anorexia nervosa patients whose menstrual cycles are not restored after weight recovery. SUMMARY: Energy availability is a theoretically satisfying and operationally controllable concept for understanding, investigating, and managing the energy dependence of reproductive function. Nutritional intervention to restore menstrual cycles in anorexia nervosa patients might be more successful if it was guided by energy availability and ovarian volume rather than energy intake and body weight.

American College of Sports Medicine position stand. The female athlete triad.

The female athlete triad (Triad) refers to the interrelationships among energy availability, menstrual function, and bone mineral density, which may have clinical manifestations including eating disorders, functional hypothalamic amenorrhea, and osteoporosis. With proper nutrition, these same relationships promote robust health. Athletes are distributed along a spectrum between health and disease, and those at the pathological end may not exhibit all these clinical conditions simultaneously. Energy availability is defined as dietary energy intake minus exercise energy expenditure. Low energy availability appears to be the factor that impairs reproductive and skeletal health in the Triad, and it may be inadvertent, intentional, or psychopathological. Most effects appear to occur below an energy availability of 30 kcal.kg(-1) of fat-free mass per day. Restrictive eating behaviors practiced by girls and women in sports or physical activities that emphasize leanness are of special concern. For prevention and early intervention, education of athletes, parents, coaches, trainers, judges, and administrators is a priority. Athletes should be assessed for the Triad at the preparticipation physical and/or annual health screening exam, and whenever an athlete presents with any of the Triad's clinical conditions. Sport administrators should also consider rule changes to discourage unhealthy weight loss practices. A multidisciplinary treatment team should include a physician or other health-care professional, a registered dietitian, and, for athletes with eating disorders, a mental health practitioner. Additional valuable team members may include a certified athletic trainer, an exercise physiologist, and the athlete's coach, parents and other family members. The first aim of treatment for any Triad component is to increase energy availability by increasing energy intake and/or reducing exercise energy expenditure. Nutrition counseling and monitoring are sufficient interventions for many athletes, but eating disorders warrant psychotherapy. Athletes with eating disorders should be required to meet established criteria to continue exercising, and their training and competition may need to be modified. No pharmacological agent adequately restores bone loss or corrects metabolic abnormalities that impair health and performance in athletes with functional hypothalamic amenorrhea.

Low energy availability in the marathon and other endurance sports.

Energy availability is the amount of dietary energy remaining after exercise training for all other metabolic processes. Excessively low energy availability impairs reproductive and skeletal health, although genetics and age may alter an individual's initial conditions and sensitivity when low energy availability is imposed. Many marathon runners and other endurance athletes reduce energy availability either (i) intentionally to modify body size and composition for improving performance; (ii) compulsively in a psychopathological pattern of disordered eating; or (iii) inadvertently because there is no strong biological drive to match energy intake to activity-induced energy expenditure. Inadvertent low energy availability is more extreme when consuming a low fat, high carbohydrate diet. Low energy availability, reproductive disorders, low bone mineral density and stress fractures are more common in female than male athletes. Functional menstrual disorders caused by low energy availability should be diagnosed by excluding diseases that also disrupt menstrual cycles. To determine energy availability (in units of kilocalories or kilojoules per kilogram of fat-free mass), athletes can record their diets and use diet analysis software to calculate energy intake, measure energy expenditure during exercise using a heart monitor and measure fat-free mass using a bioelectrical impedance body composition scale. All are commercially available at consumer prices.

Energy and carbohydrate for training and recovery.

Soccer players should achieve an energy intake that provides sufficient carbohydrate to fuel the training and competition programme, supplies all nutrient requirements, and allows manipulation of energy or nutrient balance to achieve changes in lean body mass, body fat or growth. Although the traditional culture of soccer has focused on carbohydrate intake for immediate match preparation, top players should adapt their carbohydrate intake on a daily basis to ensure adequate fuel for training and recovery between matches. For players with a mobile playing style, there is sound evidence that dietary programmes that restore and even super-compensate muscle glycogen levels can enhance activity patterns during matches. This will presumably also benefit intensive training, such as twice daily practices. As well as achieving a total intake of carbohydrate commensurate with fuel needs, the everyday diet should promote strategic intake of carbohydrate and protein before and after key training sessions to optimize the adaptations and enhance recovery. The achievement of the ideal physique for soccer is a long-term goal that should be undertaken over successive years, and particularly during the off-season and pre-season. An increase in lean body mass or a decrease in body fat is the product of a targeted training and eating programme. Consultation with a sports nutrition expert can assist soccer players to manipulate energy and nutrient intake to meet such goals. Players should be warned against the accidental or deliberate mismatch of energy intake and energy expenditure, such that energy availability (intake minus the cost of exercise) falls below 125 kJ (30 kcal) per kilogram of fat-free mass per day. Such low energy availability causes disturbances to hormonal, metabolic, and immune function.

Special populations: the female player and the youth player.

Females and youth are frequently described as "special" populations in football literature, but together these two populations outnumber male players. What makes females "special" is that they tend to eat less when training and competing than their male counterparts, leading to lower intakes of energy, carbohydrate, and some nutrients. Youth football players are special in regard to energy and nutrient requirements to promote growth and development, as well as to fuel sport. There is limited research on the dietary habits of these two populations, but the available literature suggests that many female and youth players need to increase carbohydrate intake, increase fluid intake, and develop dietary habits to sustain the demands of training and competition.