Bjoern Buehring

Glucocorticoid-induced osteoporosis: an update on effects and management.

Glucocorticoids remain a cornerstone of guideline-based management of persistent asthma and allergic diseases. Glucocorticoid-induced osteoporosis (GIO) is the most common iatrogenic cause of secondary osteoporosis and an issue of concern for physicians treating patients with inhaled or oral glucocorticoids either continuously or intermittently. Patients with GIO experience fragility fractures at better dual-energy x-ray absorptiometry T-scores than those with postmenopausal or age-related osteoporosis. This might be explained, at least in part, by the effects of glucocorticoids not only on osteoclasts but also on osteoblasts and osteocytes. Effective options to detect and manage GIO exist, and a management algorithm has been published by the American College of Rheumatology to provide treatment guidance for clinicians. This review will summarize GIO epidemiology and pathophysiology and assess the role of inhaled and oral glucocorticoids in asthmatic adults and children, with particular emphasis on the effect of such therapies on bone health. Lastly, we will review the American College of Rheumatology GIO guidelines and discuss diagnostic and therapeutic strategies to mitigate the risk of GIO and fragility fractures.

What's in a name revisited: should osteoporosis and sarcopenia be considered components of "dysmobility syndrome?"

Sarcopenia and osteoporosis are age-related declines in the quantity and quality of muscle and bone respectively, with shared pathogeneses and adverse health consequences. Both absolute and relative fat excess, i.e., obesity and sarcopenic obesity, contribute to disability, falls, and fractures. Rather than focusing on a single component, i.e., osteoporosis, sarcopenia, or obesity, we realized that an opportunity exists to combine clinical factors, thereby potentially allowing improved identification of older adults at risk for disability, falls, and fractures. Such a combination could be termed dysmobility syndrome, analogous to the approach taken with metabolic syndrome. An arbitrary score-based approach to dysmobility syndrome diagnosis is proposed and explored in a small cohort of older adults. Further evaluation of such an approach in large population-based and prospective studies seems warranted.

Beyond FRAX®: It's Time to Consider “Sarco-Osteopenia”

A dictionary definition of ‘‘frail’’ includes easily broken, fragile, and physically weak, the descriptors often used to explain osteoporotic bone. However, physicians recognize that it is not simply bone abnormalities, but rather the simultaneous presence of muscle and bone weakness, often associated with overall frailty, which contributes to high fracture risk in their older patients. How can clinicians optimally identify which patients are at highest risk for fracture? Bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has been a key advance in care for patients at risk for fragility fracture. Although DXA-measured BMD is excellent at identifying those at higher risk, its use alone is not optimal and including clinical factors improves fracture risk estimation. To this end, the World Health Organization (WHO) FRAX tool improves targeting of pharmacologic therapy by combining clinical risk factors and estimating 10-yr fracture probability. Clearly, fracture risk increases dramatically with advancing age (1); that this risk markedly increases at the same BMD is easily quantified using FRAX (depicted in Fig. 1). We recognize the major contribution of FRAX to patient care and further suggest, in addition to using FRAX , that the time has come for clinicians to consciously recognize muscle weakness as a

A Case of an Unusual Subtrochanteric Fracture in a Patient Receiving Denosumab

OBJECTIVE Bisphosphonates are the most common class of medications used to treat osteoporosis. Their widespread use has uncovered rare complications, including atypical femoral fractures (AFF). The pathogenesis of AFF is incompletely understood; however, if oversuppression of bone remodeling contributes to AFF, it is plausible that other potent antiresorptive agents, such as denosumab, could be associated with AFF as well. METHODS We report a case of an 81-year-old woman with densitometric osteopenia, chronic kidney disease, and hyperparathyroidism, who was initiated on denosumab for elevated fracture risk. Approximately 6 months after her initial denosumab injection, she developed severe right groin and thigh pain without prior trauma. RESULTS A femoral radiograph was normal, without cortical thickening, but a magnetic resonance imaging revealed a transverse subtrochanteric insufficiency fracture with a medial defect involving 25% of the femoral cortex. She did not receive any further doses of denosumab. Bone turnover markers did not suggest oversuppression. Her fracture was treated conservatively with nonweight bearing status with resultant full recovery. CONCLUSION This fracture does not meet the current definition of an AFF as, for that definition, a lateral femoral location is required. This case does not provide conclusive evidence for a causal relationship between treatment with denosumab and this unusual fracture. It clearly illustrates, however, the occurrence of an unusual, nontraumatic subtrochanteric fracture in a patient treated with the potent antiresorptive agent denosumab with many features in common with bisphosphonate-associated AFF.

Vertebral fracture assessment: impact of instrument and reader

PurposeMany osteoporotic vertebral fractures are not clinically recognized but increase fracture risk. We hypothesized that a newer generation densitometer increases the number of evaluable vertebrae and vertebral fractures detected. We also explored the impact of reader experience on vertebral fracture assessment (VFA) interpretation.MethodsVFA images obtained using Prodigy and iDXA densitometers in 103 older adults were evaluated for vertebral visualization and fracture presence in the T4–L5 region. A “true” read for each densitometer was achieved by consensus. If readers disagreed, the evaluation of a third expert physician was taken as true. Main outcomes were evaluable vertebrae, vertebral fractures, and intrareader/interreader reproducibility.ResultsUsing the “true” reads, 92% of vertebrae were visualized on iDXA and 76% on Prodigy. Numerically, more fractures were identified with iDXA; the “true” reads found 43 fractures on iDXA and 21 on Prodigy. The experienced reader had better intrareader and interreader reproducibility than the inexperienced reader when compared with the “true” read.ConclusionsUsing the newer iDXA densitometer for VFA analysis improves vertebral body visualization and fracture detection. Training and experience enhance result reproducibility.

Tongue Strength Is Associated with Jumping Mechanography Performance and Handgrip Strength but Not with Classic Functional Tests in Older Adults

To determine whether classic muscle function tests and jumping mechanography (JM) are related to tongue strength.

Jumping Mechanography: A Potential Tool for Sarcopenia Evaluation in Older Individuals

Muscular function declines with advancing age and is associated with increased risk for falls and fragility fractures. No single methodology ideally quantitatively evaluates this decline. Jumping mechanography (JM) may prove useful to quantitatively measure muscular function in older adults. This study begins to evaluate the safety of JM and the relationship of jump power and lean mass in older adults. Eighty adults, 40 aged 20-30 yr and 40 aged 60 yr or older, distributed equally by gender, participated. They performed countermovement jumps to assess jump power and height. Self-reported pain before and after jumping and need for assistance was recorded. In the older group, dual-energy X-ray absorptiometry was used to measure bone mineral density, to estimate lean body mass, and to determine vertebral fracture status. Jumping was well tolerated without injury or increased pain. No new vertebral fractures occurred with jumping in the older group. Young individuals had greater jump power and height compared with the older group. Older age was negatively correlated, whereas lean mass positively correlated with jump power and height. JM appears to be a safe and potentially useful method to assess muscular function in older adults.

Myostatin – The Holy Grail for Muscle, Bone, and Fat?

Myostatin, a member of the transforming growth factor beta (TGF-β) superfamily, was first described in 1997. Since then, myostatin has gained growing attention because of the discovery that myostatin inhibition leads to muscle mass accrual. Myostatin not only plays a key role in muscle homeostasis, but also affects fat and bone. This review will focus on the impact of myostatin and its inhibition on muscle mass/function, adipose tissue and bone density/geometry in humans. Although existing data are sparse, myostatin inhibition leads to increased lean mass and 1 study found a decrease in fat mass and increase in bone formation. In addition, myostatin levels are increased in sarcopenia, cachexia and bed rest whereas they are increased after resistance training, suggesting physiological regulatory of myostatin. Increased myostatin levels have also been found in obesity and levels decrease after weight loss from caloric restriction. Knowledge on the relationship of myostatin with bone is largely based on animal data where elevated myostatin levels lead to decreased BMD and myostatin inhibition improved BMD. In summary, myostatin appears to be a key factor in the integrated physiology of muscle, fat, and bone. It is unclear whether myostatin directly affects fat and bone, or indirectly via muscle. Whether via direct or indirect effects, myostatin inhibition appears to increase muscle and bone mass and decrease fat tissue—a combination that truly appears to be a holy grail. However, at this time, human data for both efficacy and safety are extremely limited. Moreover, whether increased muscle mass also leads to improved function remains to be determined. Ultimately potential beneficial effects of myostatin inhibition will need to be determined based on hard outcomes such as falls and fractures.

Changes in lower extremity muscle function after 56 days of bed rest

Preservation of muscle function, known to decline in microgravity and simulation (bed rest), is important for successful spaceflight missions. Hence, there is great interest in developing interventions to prevent muscle-function loss. In this study, 20 males underwent 56 days of bed rest. Ten volunteers were randomized to do resistive vibration exercise (RVE). The other 10 served as controls. RVE consisted of muscle contractions against resistance and concurrent whole-body vibration. Main outcome parameters were maximal isometric plantar-flexion force (IPFF), electromyography (EMG)/force ratio, as well as jumping power and height. Measurements were obtained before and after bed rest, including a morning and evening assessment on the first day of recovery from bed rest. IPFF (-17.1%), jumping peak power (-24.1%), and height (-28.5%) declined (P < 0.05) in the control group. There was a trend to EMG/force ratio decrease (-20%; P = 0.051). RVE preserved IPFF and mitigated the decline of countermovement jump performance (peak power -12.2%; height -14.2%). In both groups, IPFF was reduced between the two measurements of the first day of reambulation. This study indicates that bed rest and countermeasure exercises differentially affect the various functions of skeletal muscle. Moreover, the time course during recovery needs to be considered more thoroughly in future studies, as IPFF declined not only with bed rest but also within the first day of reambulation. RVE was effective in maintaining IPFF but only mitigated the decline in jumping performance. More research is needed to develop countermeasures that maintain muscle strength as well as other muscle functions including power.

Dual-Energy X-Ray Absorptiometry Measured Regional Body Composition Least Significant Change: Effect of Region of Interest and Gender in Athletes

Dual-energy X-ray absorptiometry (DXA) is widely used to evaluate body composition in athletes. Knowledge of measurement precision is essential for monitoring body composition changes over time. This study begins characterizing DXA body composition precision in 60 (30 males and 30 females) Division 1 athletes focusing on gender, regional, and tissue type differences. Two total body scans with repositioning between were performed on the same day. Least significant change (LSC) for the root-mean-square deviation (LSCRMSD) and the percent coefficient of variation (LSC%CV) for total, lean, and fat mass was calculated for 6 regions of interest. The effect of gender, region, tissue type, and mass on the standard deviation (SD) and percent coefficient of variation (%CV) between the 2 scans was evaluated using repeated measures regression analysis. Statistically significant effects of gender, region, tissue type, and mass on SD and %CV were noted. To generalize, a nonlinear positive relationship between LSCRMSD and mass and a nonlinear negative relationship between LSC%CV and mass were observed. In conclusion, DXA body composition LSC varies among genders, regions, tissues, and mass. As such, when evaluating serial body composition in athletes, especially if assessing regional change, knowledge of precision in individuals of similar body size and gender to the population of interest is needed.