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Research Article | Volume 8 Issue 1 (None, 2022) | Pages 75 - 80
Assessment of Changes in Bone Mineral Density Following Pelvic Radiotherapy in Patients with Cervical Cancer: A Prospective Study
1
Assistant Professor, Department of Radiation Oncology, Konaseema Institute of Medical Sciences, Amalapuram, Andhra Pradesh, India.
Under a Creative Commons license
Open Access
Received
Feb. 17, 2022
Revised
Feb. 25, 2022
Accepted
March 2, 2022
Published
March 10, 2022
Abstract
Background: Pelvic radiotherapy is a standard treatment modality for patients with carcinoma cervix, particularly in locally advanced stages. Although radiotherapy improves survival outcomes, exposure of pelvic bones to ionizing radiation may lead to reduction in bone mineral density (BMD) and increase the risk of osteopenia, osteoporosis, and insufficiency fractures. Early identification of treatment-related bone loss is important to prevent long-term skeletal complications and improve quality of life among cervical cancer survivors. Aim: To assess the changes in bone mineral density following pelvic radiotherapy in patients with cervical cancer. Materials and Methods: This prospective observational study was conducted in the Department of Radiology at Konaseema Institute of Medical Sciences, Amalapuram over a period of 18 months from May 2019 to January 2021. A total of 60 patients with histopathologically confirmed carcinoma cervix undergoing pelvic radiotherapy were included in the study. Bone mineral density was measured using Dual-Energy X-ray Absorptiometry (DEXA) at the lumbar spine, femoral neck, and total hip. Baseline BMD was recorded before initiation of radiotherapy and follow-up assessment was performed 6 months after completion of treatment. BMD values were expressed as T-scores and categorized according to World Health Organization criteria. Statistical analysis was performed using the paired t-test, and a p-value <0.05 was considered statistically significant. Results: Among the 60 patients included in the study, the majority (36.7%) were in the 50–59 years age group. Baseline BMD assessment showed that 53.3% of patients had normal bone density, while 33.3% had osteopenia and 13.4% had osteoporosis. Following pelvic radiotherapy, the proportion of patients with normal BMD decreased to 33.3%, whereas osteopenia increased to 43.3% and osteoporosis increased to 23.4%. The mean T-score declined from −0.92 ± 0.84 before treatment to −1.58 ± 0.96 after treatment, demonstrating a statistically significant reduction in bone mineral density (p = 0.001). The lumbar spine and femoral neck showed the most significant reduction in BMD. Conclusion: Pelvic radiotherapy in patients with carcinoma cervix is associated with a significant reduction in bone mineral density, increasing the risk of osteopenia and osteoporosis. Baseline BMD assessment and periodic monitoring are recommended for early detection and management of radiation-induced bone loss to improve long-term outcomes in cervical cancer survivors.
Keywords
INTRODUCTION
Cervical cancer is one of the most common malignancies affecting women worldwide and remains a major public health problem, particularly in developing countries such as India. According to the World Health Organization, cervical cancer contributes significantly to cancer-related morbidity and mortality among women, with a large proportion of cases being diagnosed at locally advanced stages that require radiotherapy as a primary component of treatment. Radiotherapy, either alone or in combination with chemotherapy, plays a crucial role in improving local tumor control and overall survival in patients with carcinoma cervix.¹ Pelvic radiotherapy involves the delivery of high doses of ionizing radiation to the cervix, uterus, parametrial tissues, and regional lymph nodes. However, adjacent normal tissues, including pelvic bones such as the sacrum, iliac bones, and femoral heads, are inevitably exposed to radiation during treatment. Ionizing radiation can adversely affect bone metabolism by damaging osteoblasts, impairing vascular supply, and increasing osteoclastic bone resorption, which may ultimately lead to a reduction in bone mineral density (BMD).² Radiation-induced bone loss has increasingly been recognized as an important late complication of pelvic irradiation. Several studies have reported that patients undergoing pelvic radiotherapy are at increased risk of developing osteopenia, osteoporosis, and pelvic insufficiency fractures. These skeletal complications may result in chronic pain, reduced mobility, and impaired quality of life among long-term cancer survivors.³ With advancements in cancer treatment and improved survival rates, the long-term adverse effects of therapy have gained considerable attention in recent years. Monitoring bone mineral density in patients undergoing pelvic irradiation is therefore essential for early detection of treatment-related bone loss and for the implementation of preventive strategies. Studies have demonstrated that periodic evaluation of BMD using Dual-Energy X-ray Absorptiometry (DEXA) can help identify patients at risk and facilitate timely intervention to reduce skeletal complications. ⁴ Despite the clinical importance of this issue, there is limited prospective data evaluating the impact of pelvic radiotherapy on bone mineral density in cervical cancer patients, especially in the Indian population. Therefore, the present study was undertaken to assess the changes in bone mineral density following pelvic radiotherapy in patients with carcinoma cervix.
MATERIALS AND METHODS
Study Design This study was designed as a prospective observational study to evaluate the changes in bone mineral density (BMD) in patients with carcinoma cervix undergoing pelvic radiotherapy. Place of Study The study was conducted in the Department of Radiology in collaboration with the Department of Radiation Oncology at Konaseema Institute of Medical Sciences, located in Amalapuram. Duration of Study The study was carried out over a period of 18 months from May 2019 to January 2021. Study Population The study population consisted of female patients diagnosed with carcinoma cervix who were planned for pelvic radiotherapy as part of their treatment protocol. Sample Size A total of 60 patients fulfilling the inclusion criteria were enrolled in the study after obtaining informed consent. Inclusion Criteria 1. Histopathologically confirmed cases of carcinoma cervix. 2. Patients planned to receive pelvic radiotherapy with or without concurrent chemotherapy. 3. Patients aged 30–70 years. 4. Patients willing to participate and provide informed consent. Exclusion Criteria 1. Patients with pre-existing metabolic bone disorders such as osteoporosis or osteomalacia. 2. Patients with a history of long-term steroid therapy. 3. Patients with bone metastasis. 4. Patients who had previously received pelvic radiotherapy. 5. Patients with severe systemic illness affecting bone metabolism. Data Collection After obtaining institutional ethical committee approval, detailed clinical history and demographic data were recorded for each patient, including age, menopausal status, stage of disease, and treatment details. Measurement of Bone Mineral Density Bone mineral density was measured using Dual-Energy X-ray Absorptiometry (DEXA) scanning, which is considered the gold standard for assessing BMD. DEXA scans were performed at the following skeletal sites: • Lumbar spine (L1–L4) • Femoral neck • Total hip Baseline BMD measurements were recorded prior to initiation of pelvic radiotherapy. Follow-up BMD assessment was performed 6 months after completion of radiotherapy to evaluate treatment-related changes. Radiotherapy Protocol All patients received external beam pelvic radiotherapy using standard treatment protocols. The total radiation dose ranged from 45–50 Gy delivered in 25 fractions over 5 weeks, followed by intracavitary brachytherapy as per institutional guidelines. Outcome Measures The primary outcome of the study was change in bone mineral density before and after pelvic radiotherapy. BMD values were expressed as T-scores and categorized according to the World Health Organization classification: • Normal: T-score ≥ −1 • Osteopenia: T-score between −1 and −2.5 • Osteoporosis: T-score ≤ −2.5 Statistical Analysis The collected data were entered into Microsoft Excel and analyzed using SPSS statistical software. Continuous variables were expressed as mean ± standard deviation, while categorical variables were expressed as frequency and percentage. Comparison between baseline and post-radiotherapy BMD values was performed using the paired t-test. A p-value <0.05 was considered statistically significant.
RESULTS
A total of 60 patients with histopathologically confirmed carcinoma cervix undergoing pelvic radiotherapy were included in the study. Bone mineral density (BMD) was assessed using DEXA scan before initiation of radiotherapy and at 6-month follow-up after completion of treatment. Table 1: Age Distribution of Study Participants Age Group (Years) Number of Patients Percentage (%) 30–39 8 13.3 40–49 16 26.7 50–59 22 36.7 ≥60 14 23.3 Total 60 100 The majority of patients (36.7%) were in the 50–59 years age group, followed by 26.7% in the 40–49 years group. Table 2: Baseline Bone Mineral Density Status Before Radiotherapy BMD Category Number of Patients Percentage (%) Normal 32 53.3 Osteopenia 20 33.3 Osteoporosis 8 13.4 Total 60 100 Before initiation of pelvic radiotherapy, 53.3% of patients had normal BMD, while 33.3% had osteopenia and 13.4% had osteoporosis. Table 3: Bone Mineral Density Status After Pelvic Radiotherapy (6-month Follow-up) BMD Category Number of Patients Percentage (%) Normal 20 33.3 Osteopenia 26 43.3 Osteoporosis 14 23.4 Total 60 100 After pelvic radiotherapy, the proportion of patients with normal BMD decreased from 53.3% to 33.3%, while osteopenia increased to 43.3% and osteoporosis increased to 23.4%. Table 4: Comparison of Mean BMD (T-Score) Before and After Radiotherapy Measurement Time Mean T-Score Standard Deviation p-value Before Radiotherapy -0.92 ±0.84 After Radiotherapy -1.58 ±0.96 0.001 Observation: There was a significant reduction in mean BMD (T-score) following pelvic radiotherapy. Statistical analysis using the paired t-test showed this reduction to be statistically significant (p < 0.05). Table 5: Site-wise Reduction in BMD After Radiotherapy Skeletal Site Mean BMD Before RT Mean BMD After RT p-value Lumbar Spine (L1–L4) -0.88 -1.52 0.002 Femoral Neck -0.95 -1.63 0.003 Total Hip -0.91 -1.59 0.004 A statistically significant reduction in BMD was observed at all measured skeletal sites, with the lumbar spine and femoral neck showing the greatest decline after pelvic irradiation.
DISCUSSION
Pelvic radiotherapy remains a cornerstone in the treatment of carcinoma cervix because of its established role in improving local control and survival. However, irradiation of the pelvic skeleton may adversely affect bone health, resulting in progressive decline in bone mineral density [BMD] and increased susceptibility to insufficiency fractures [8-10,12,13]. In the present prospective study, a significant reduction in BMD was observed following pelvic radiotherapy, highlighting an important survivorship concern in women treated for cervical cancer. In the present study, most patients belonged to the 50–59-year age group. This observation is clinically relevant because women in this age range are often postmenopausal and therefore already vulnerable to accelerated bone loss. The diagnostic framework for osteopenia and osteoporosis is based on BMD-derived T-scores, as described by Kanis et al. [7], and postmenopausal bone loss remains a major determinant of skeletal fragility. The coexistence of age-related bone loss and radiation exposure may therefore increase the likelihood of treatment-related skeletal complications [10,12,14]. Baseline BMD assessment in our study showed that 46.7% of patients had either osteopenia or osteoporosis before initiation of radiotherapy. This finding suggests that a substantial proportion of women with cervical cancer may already have compromised skeletal health at presentation. Such baseline vulnerability is important because patients entering treatment with lower BMD may be more likely to develop clinically significant bone loss after irradiation. Current osteoporosis guidelines also emphasize the importance of identifying high-risk individuals early, particularly postmenopausal women and those with additional risk factors for fragility fractures [14]. The principal finding of the present study was a statistically significant decline in BMD after pelvic radiotherapy. This is in agreement with the study by Nabil et al. [9], who demonstrated a reduction in BMD in patients with gynecological malignancies following pelvic irradiation. Radiation-induced skeletal injury has been attributed to multiple mechanisms, including direct damage to osteoblasts, microvascular compromise, impairment of bone remodeling, and increased bone fragility [8,15]. Experimental evidence from Willey et al. [15] further supports the concept that radiation exposure can induce early osteoporotic changes, and that antiresorptive treatment may mitigate such damage. In our study, the proportion of patients with osteopenia increased from 33.3% to 43.3%, while the proportion with osteoporosis increased from 13.4% to 23.4% after radiotherapy. These findings are clinically meaningful because even a modest decline in BMD may translate into a greater risk of skeletal morbidity. Oh et al. [10] reported that pelvic radiotherapy for cervical cancer was associated with an increased incidence of pelvic insufficiency fractures, particularly in women with pre-existing risk factors for weakened bone. Similar observations were reported by Tokumaru et al. [13], who identified insufficiency fractures as an important late complication after pelvic radiotherapy for uterine cervical cancer. Site-wise analysis in the present study showed that lumbar spine and femoral neck BMD declined significantly after treatment. This pattern is biologically plausible because these regions contain a high proportion of trabecular bone, which is metabolically active and more vulnerable to structural injury. Kim et al. [8] described radiation-induced bone changes and emphasized that irradiated bone becomes more susceptible to weakening and fracture. Since the vertebrae and proximal femur are major weight-bearing structures, loss of BMD at these sites may have substantial consequences for mobility, pain, and long-term quality of life. The present findings also underscore the growing importance of survivorship care in cervical cancer. As treatment outcomes improve, long-term adverse effects such as osteoporosis and pelvic insufficiency fractures deserve greater clinical attention. Schmeler et al. [12] documented pelvic fractures after radiotherapy for cervical cancer, reinforcing the need for heightened awareness of skeletal complications in survivors. Likewise, Oh et al. [10] and Tokumaru et al. [13] showed that fracture risk after pelvic radiotherapy is not negligible and may be underrecognized in routine follow-up. These findings support the need for preventive and therapeutic strategies aimed at preserving bone health in women undergoing pelvic radiotherapy. Osteoporosis management guidelines recommend risk assessment, BMD evaluation, adequate calcium and vitamin D intake, weight-bearing exercise, and pharmacologic therapy in selected high-risk patients [11,14]. Reid [11] highlighted that osteoporosis therapies can reduce bone loss and fracture risk, while Willey et al. [15] provided experimental support for the protective effect of bisphosphonates against radiation-induced bone damage. Therefore, early screening and timely intervention may be beneficial in reducing skeletal morbidity in this patient population. The present study has certain limitations. The sample size was relatively small, and follow-up was limited to six months after radiotherapy. Because radiation-related skeletal complications may continue to evolve over a longer duration, extended prospective studies with larger cohorts are needed to better define the magnitude, timing, and clinical consequences of post-radiotherapy bone loss. Nevertheless, the current study adds to the growing body of evidence showing that pelvic radiotherapy is associated with measurable deterioration in bone health and supports the inclusion of BMD surveillance in the follow-up of cervical cancer patients [9,10,12,13].
CONCLUSION
The present prospective study demonstrates that pelvic radiotherapy in patients with carcinoma cervix is associated with a significant reduction in bone mineral density. A substantial increase in the prevalence of osteopenia and osteoporosis was observed following treatment. The lumbar spine and femoral neck were the most affected skeletal sites. These findings highlight the importance of baseline BMD assessment and periodic monitoring in patients undergoing pelvic radiotherapy. Early detection of bone loss and timely implementation of preventive measures may help reduce the risk of osteoporosis and insufficiency fractures, thereby improving long-term quality of life in cervical cancer survivors.
REFERENCES
1.Baxter NN, Habermann EB, Tepper JE, Durham SB, Virnig BA. Risk of pelvic fractures in older women following pelvic irradiation. JAMA. 2005;294(20):2587–2593. 2.Berrington de González A, Curtis RE, Kry SF, Gilbert E, Lamart S, Berg CD, et al. Proportion of second cancers attributable to radiotherapy treatment in adults. Lancet Oncol. 2011;12(4):353–360. 3.Blomlie V, Rofstad EK, Skovlund E, Talle K, Sundfør K, Winderen M, et al. Pelvic insufficiency fractures after radiation therapy for gynecologic malignancies. Acta Radiol. 1996;37(5):665–670. 4.Blomlie V, Rofstad EK, Talle K, et al. Incidence of radiation-induced insufficiency fractures after treatment of cervical cancer. Radiology. 1993;188(1):241–244. 5.Chiarelli AM, Kirsh VA, Klar NS, et al. Influence of radiation therapy on bone mineral density and fracture risk in women treated for pelvic malignancies. Osteoporos Int. 2011;22(2):673–680. 6.Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: GLOBOCAN estimates of incidence and mortality. Int J Cancer. 2015;136(5):E359–E386. 7.Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9(8):1137–1141. 8.Kim HJ, Boland PJ, Meredith DS, Lis E, Zhang Z, Shi W, et al. Radiation-induced bone changes and risk of fracture after radiotherapy. Clin Orthop Relat Res. 2013;471(3):1099–1107. 9.Nabil F, Samy A, El-Sherif A. Effect of pelvic radiotherapy on bone mineral density in patients with gynecological malignancies. Clin Oncol. 2014;26(9):555–560. 10.Oh D, Huh SJ, Nam H, Park W, Han Y. Pelvic insufficiency fracture after pelvic radiotherapy for cervical cancer: analysis of risk factors. Int J Radiat Oncol Biol Phys. 2008;70(4):1183–1188. 11.Reid IR. Short-term and long-term effects of osteoporosis therapies. Nat Rev Endocrinol. 2015;11(7):418–428. 12.Schmeler KM, Jhingran A, Iyer RB, Sun CC, Eifel PJ, Soliman PT. Pelvic fractures after radiotherapy for cervical cancer. Cancer. 2010;116(3):625–630. 13.Tokumaru S, Toita T, Oguchi M, et al. Insufficiency fractures after pelvic radiotherapy for uterine cervical cancer. Radiother Oncol. 2012;103(3):364–367. 14.Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2016;22(Suppl 4):1–42. 15.Willey JS, Livingston EW, Robbins ME, Bourland JD, Tirado-Lee L, Smith-Sielicki H. Risedronate prevents early radiation-induced osteoporosis in mice. Radiat Res. 2010;173(3):330–339.
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