Osteopenic fractures, the importance of applying gender-specific bone mineral density thresholds in identifying hip fracture at-risk populations, and comments on the article of Xu et al.

Osteoporosis is a systemic skeletal disease characterised by a reduction in bone mass and qualitative skeletal changes that cause an increase in bone fragility and a higher fracture risk. The clinical significance of osteoporosis lies in the occurrence of fragility fractures (FFx). In the literature, it has often been described in a way giving the perception that, when an older person suffers from a fracture, this fracture is either an osteoporotic fracture or is associated with normal bone strength. We argued that the concept of ‘osteopenic fracture’ should be used much more often, as many of the fractures among older persons are indeed ‘osteopenic fractures’. Low-energy trauma induced vertebral fractural deformities are common among young subjects with normal bone strength (1,2). Traumatological literature shows that distal forearm, proximal humerus, and vertebral fractures can occur in young subjects with normal bone strength and with low energy trauma. As shown in Figure 1 (3-8), while osteoporosis can be assumed to be uncommon among young and middle-aged populations, on average more than 1/3 of humerus fractures and distal forearm fractures are low-energy fractures (with energy level no more than a fall from a standing height, often termed as ‘moderate trauma’ in traumatological literature). Moreover, the proportion of low-energy humerus and distal forearm fractures appeared to be higher among females. This could be due to combination of males are more likely involved with high energy trauma incidents, and males may have stronger bones than their female counterparts. Among old females, compared with the cases of hip fracture, distal forearm fracture occurs at ‘younger’ age and ‘higher’ bone mineral density (BMD) (9,10). Inter-ethnic group prevalence difference of distal forearm fracture also does not appear to follow the prevalence difference pattern of hip fracture (9). Compared with the cases with hip fracture, distal forearm and proximal humerus fractures are more likely associated with a ‘higher’ energy level (Figure 2). Compared with younger populations, fracture prevalence of distal forearm and proximal humerus increases very substantially among older populations. However, for distal forearm fractures and proximal humerus fractures among the elderly, while some are truly osteoporotic fractures, some are fractures with age-appropriate bone strength, and some can be osteopenic fractures.

Figure 1 Proportions of low energy trauma induced humeral fracture and distal radius fracture among young populations. This proportion appears to be higher among females than among males. Humeral fracture data are from (A-C) Rose et al. (3), Wong (4), and Bergdahl et al. (5); and distal radius fracture data are from (D-F) Lindau et al. (6), Brogren et al. (7), and Moloney et al. (8).

Figure 2 Compared with cases with hip fracture, distal forearm fracture is more likely associated with a ‘higher’ trauma energy level. (A) A standing person; (B,C) a fall will lead to a distal forearm (wrist) hitting the ground; (D) a fall will lead to a buttock hitting the ground. The net external force equals the change in momentum of a system divided by the time over which it changes. If we assume that the angular velocity is the same for a forward fall (B,C) as for a backward fall (D), since the radius r1>r2, velocity at the impact with the ground for a forward fall (v1) will be larger than that for a backward fall (v2, v1>v2) (E). In addition, due to the buffering of muscle and fat at the buttock, the impact time for backward fall (t2) will be larger than that of forward fall (t1, t1<t2). Thence, the impact force for a forward fall (B', F1=v1/t1) will be larger than that of backward fall (D', F2=v2/t2).

Among all FFx, hip fracture incurs the greatest morbidity, mortality, and costs. Though the prevalence of hip FFx is lower among men than among women, multiple reports described that, once hip FFx occurs, post-fracture mortality is substantially higher among men than among women. In a study based on 2000–2011 data of California, USA, males were nearly two times more likely to die within 30 days of a hip FFx than females [odds ratio 1.79, 95% confidence interval (CI): 1.72–1.86, P<0.001] and were also more likely to die at other assessed time points (90 and 365 days) (11). In a Danish study published in 2010, compared with the general older population, the 1-year mortality after hip fracture increased by 27.2% in male patients and by 17.1% in female patients (12). In a Hong Kong study published in 2016, mortality at 1 year after hip fracture was 27% in males and 15% in females (13). In a study of mainland China published in 2022, mortality at 1 year after hip fracture was 19.63% in males and 13.46% in females (14). Some studies suggest that males tend to suffer from hip FFx at a younger age than females (15). In addition to high mortality, many hip FFx patients with poor functional recovery are unable to resume their pre-fracture function with a consequent deterioration in quality of life (16-19). With an aging population and increasing longevity, the hip fracture rate is expected to increase continuously. It is important to identify hip FFx high risk populations both among older females and among older males. A fall involving a hip fracture is also associated with a larger ‘contact surface’ than a fall involving the distal forearm, and also the hip region has more soft tissues and muscles functioning as a cushion (Figure 2). While it is not necessary that all low-energy traumas among older population are osteoporotic fractures, hip fractures are most likely to be associated with a lower energy level, and low-energy induced hip fracture suggests that the bone strength is indeed much compromised. We can make a hypothesis that in vivo imaging would likely be able to detect such a weakness of the upper femur when appropriate methodologies and criteria are applied.

Recently, we reported the observation that older men suffer from hip FFx at femoral neck (FN) T-score approximately 0.5–0.6 higher than older women (15). While the mean hip FFx FN dual-energy X-ray absorptiometry (DXA) T-score of around −2.9 for women lies below −2.5, the mean hip FFx FN T-score of around −2.33 for men lies above −2.5. This is likely associated with that older male populations have a higher mean T-score than older female populations. We proposed a new category of low BMD status, osteofrailia, for older Caucasian men with T-score ≤−2 (T-score ≤−2.1 for older Chinese men) who are likely to suffer from hip FFx (Figure 3) (15). Considering the mean values and the standard deviations of FN T-score of the hip FFx patients in various reports (15), at the timepoint of the fracture, approximately 2/3 of the hip FFx patients would have either FN osteoporosis for women or FN osteofrailia for men. The recent article authored by Xu et al. (20) supports our observations described in (15). This case-control study of Xu et al. included patients over the age of 65 years admitted to a hospital for hip FFx. Subjects without FFx from their healthcheck examination center or outpatient center were included as a control group. Age and gender were matched to eliminate potential confounding factors. BMD at the FN and intertrochanteric (IT) regions of the hip FFx group and of control group were measured using quantitative computed tomography (QCT). After matching for age and gender, 68 female patients (FN FFx n=34, IT FFx n=34), 28 male patients (FN FFx n=14, IT FFx n=14), and their controls (n=34 female, n=14 male) were included. The patients of FN FFx group aged between 65 and 91 years (average age 82.42±6.11 years), the IT FFx group aged between 67 and 92 years (average age 82.77±5.60 years), and the control group aged between 67 and 92 years (average age 83.15±5.91 years). Figure 4 shows, for both FN FFx and IT FFx, men fractured at a higher QCT BMD than women. The male vs. female difference in FFx patients approximately parallels the male vs. female difference of the control subjects. Interestingly, the gradient of this male vs. female difference in FN QCT BMD is very similar to the gradient of mean male vs. female difference in FN/total hip (TH) DXA T-score approximately from the data in Figure 4A (21-24), with the difference of 58 mg/mL QCT BMD difference being equivalent to T-score difference of 0.587.

Figure 3 The FN BMD distribution of US Caucasians and thresholds to define osteoporosis/osteofrailia. The mean FN T-score among US older Caucasian community men is −1.241, the mean FN T-score among US older Caucasian community women is −1.717, and the T-score difference is 0.476 (denoted with a green dotted rectangle). Red line: the T-score to define osteoporosis in women. Blue line: the T-score to define osteofrailia in men. The osteoporosis T-score threshold of −2.5 for women and the osteofrailia T-score threshold of −2.0 for men are together denoted with a green dotted rectangle. T-score =−2.91 and T-score =−2.33 are the approximately estimated mean hip fracture T-scores for women and men respectively (denoted with a green dotted rectangle). This figure is adapted from the study by Wáng et al. (15) with permission. FN, femoral neck; BMD, bone mineral density.

Figure 4 Older males suffer from hip FFx at a higher T-score or QCT BMD than older females. (A) Older East Asian males suffer from hip FFx at a higher T-score than older East Asian females. The data were based on a systematic literature search as described in (15). Contralateral hip DAX BMD was measured at the timepoint of the hip FFx accident [Li et al. (21), Lee et al. (22), Gani et al. (23), Ho et al. (24)]. (B) FN QCT for FN FFx (FNF) patients. QCT BMD male vs. female difference for the patients is similar to the QCT BMD male vs. female difference for the control subjects (no-FFx). The dotted red line (DXA assumed) denotes the mean value of male vs. female difference presented in (A), and with female value normalized to be 200. QCT BMD male vs. female differences are similar in trend to the T-score male vs. female difference shown in (A). (C) IT QCT for IT FFx (ITF) patients. QCT BMD male vs. female difference for the patients is similar to the QCT BMD male vs. female difference for the control subjects (no-FFx). The meaning of the dotted red line is the same as that in (B). (D) The FN and IT measurement regions of interest for the results shown in (B,C). (B-D) are based on Xu et al. (20). TH, total hip; FN, femoral neck; FNF, femoral neck fracture; FFx, fragility fractures; DXA, dual-energy X-ray absorptiometry; QCT, quantitative computed tomography; BMD, bone mineral density; ITF, intertrochanteric fragility fracture; IT, intertrochanteric.

Another feature in Figure 4 is that there was a good separation between the QCT BMD measures of the control subjects and those of the patients, both for FN FFx and for IT FFx. If we assume their QCT BMD data follow normal distribution, simulated values considering the mean and SD of the data can be generated. We conducted simulation 6–7 times for each value, and we also assumed that FN FFx and IT FFx each counted for 50% of hip FFx (22,25), and the results are shown in Figure 5A-5C. Figure 5 shows the differentiation between hip FFx patients and control subjects is better when males’ and females’ hip BMD measures are separated than when males’ and females’ hip BMD measures are mixed. This is consistent with the data of Cheng et al. (26) shown in Figure 5D,5E. While results of Xu et al. (20) confirm an advantage in applying gender-specific BMD thresholds for identifying female and male at-risk patients, how generalizable of their good performance of QCT BMD measure in separating at-risk patients and controls remains unknown.

Figure 5 The differentiation between hip FFx patients and control subjects is better when males’ and females’ hip BMD measures are separated than when males’ and females’ hip BMD measures are mixed. (A) Simulated females’ FN results based on Xu et al. (20). (B) Simulated males’ FN results based on Xu et al. (C) Simulated FN results with females’ and males’ measures mixed, based on Xu et al. (20). The proportion of female patients was assumed to be 61.8% and the proportion of male patients was assumed to be 38.2%. In (A-C), the values described in the study by Xu et al. (20) were assumed to follow normal distribution, and the prevalence of FN FFx and prevalence of IT FFx were assumed to be the same (22,25). (D) Mixed females’ and males’ results for FN QCT trabecular BMD, based on Cheng et al. (26). (E) Mixed females’ and males’ results for FN QCT cortical BMD, based on Cheng et al. (26). (F) The FN measurement ROIs for the results shown in (D,E). Blue ROI is for trabecular BMD, and orange ROIs are for cortical BMD. The measure ROI for (A-C) is already shown in Figure 4D. FN, femoral neck; QCT, quantitative computed tomography; BMD, bone mineral density; FFx, fragility fractures; M, male; F, female; IT, intertrochanteric; ROI, regions of interest.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2379/coif). Y.X.J.W. serves as the Editor-in-Chief of Quantitative Imaging in Medicine and Surgery. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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