Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.
Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
Clin Orthop Relat Res. 2021 Nov 1;479(11):2493-2501. doi: 10.1097/CORR.0000000000001842.
Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect.
QUESTIONS/PURPOSES: (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma?
We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals.
Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity.
Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture.
Level III, therapeutic study.
原发性骨肉瘤患者的新辅助化疗可提高生存率，但也会导致包括骨骼在内的各种器官的副作用。由于化疗或活动受限，骨矿物质密度（BMD）可能会降低。与未接受此类治疗的患者相比，这会导致骨折风险更高。BMD 的变化本身并不能解释骨折的倾向。研究骨的微观结构变化可能有助于了解其影响。
问题/目的：（1）接受过骨肉瘤治疗（20 年以上）的患者是否存在低 BMD？（2）这些患者是否比没有骨肉瘤的对照组更容易发生骨折？（3）接受高级别骨肉瘤治疗的患者与从未患有骨肉瘤的个体之间，骨微观结构有何差异？
我们联系了 48 名接受过骨肉瘤治疗并参加过早期研究的患者。这些患者接受了包括化疗在内的多模式治疗，时间超过 20 年。在原始患者组中，有 60%（48 名中的 29 名）缺失，剩下的 40%（48 名中的 19 名）可纳入本研究；所有 19 名均同意参加。这 19 名患者中有 9 名男性和 10 名女性，平均年龄为 46±4 岁，从手术到检查的平均时间为 28±3 年。BMD 通过双能 X 射线吸收法测量，通过问卷调查评估任何骨折病史。此外，还进行了高分辨率外周定量 CT 检查，以比较两组在皮质和小梁面积、皮质和小梁厚度、皮质孔隙率和内皮质周长等方面的微观结构变化。对照组的参与者是从一个由 499 名健康成年男女组成的基于人群的随机样本中选择的。进入本研究没有将骨质疏松症或低 BMD 作为排除标准；然而，对照组的参与者是根据正常 BMD（即脊柱和臀部的 T 评分均大于-1.0）选择的。此外，参与者还根据年龄和性别进行了匹配。使用 Wilcoxon 秩和检验比较连续变量，使用卡方检验比较分类变量，评估患者与对照组之间的差异。进行了多元回归分析。使用残差的直方图和分位数-分位数图检查模型假设。
19 名接受骨肉瘤治疗的患者中，有 12 名（8 名患者）存在骨质疏松症，4 名（4 名患者）存在骨质疏松症。与对照组相比，接受骨肉瘤治疗的患者（19 名患者中有 11 名）报告的骨折发生率更高（19 名对照组中有 2 名；p<0.001）。在所有微观结构参数中，仅患者的内皮质周长（75±15mm 比 62±18mm；p=0.04）大于对照组；我们没有发现两组在皮质和小梁面积、皮质和小梁厚度或皮质孔隙率方面存在差异。
尽管接受骨肉瘤治疗的患者存在骨质疏松或骨质疏松症，且骨折发生率高于对照组，但我们无法通过高分辨率外周定量 CT 确认微观结构参数存在差异。因此，在我们接受骨肉瘤治疗的患者中，骨折比例的增加似乎不是骨几何形状和微观结构参数引起的。在我们了解骨肉瘤患者化疗相关的骨变化之前，我们建议患者定期进行 BMD 检测，并建议医生考虑对低 BMD 的患者进行骨质疏松症治疗。这些数据可能为未来研究化疗与骨微观结构之间的关系提供动力。
III 级，治疗性研究。
