Radiotherapy-Associated Pelvic Insufficiency Fracture Treated by Romosozumab: Course of L1 and L5 Vertebral Body CT Attenuation

Abstract Background: Radiotherapy is a risk factor for osteoporosis and insufficiency fractures via osteoblast apoptosis and vascular injury. PTH analogs teriparatide and abaloparatide are contraindicated in patients with prior exposure to radiotherapy crossing bone due to the increased risk of osteosarcoma. Patients with radiotherapy-associated fractures or osteoporosis were eligible only for antiresorptive agents until romosozumab was recently FDA-approved. Current International Society for Clinical Densitometry (ISCD) guidelines include assessment of “opportunistic CT” as a surrogate for DXA scan using L1 vertebral body attenuation: >150 Hounsfield units (HU) is normal and <100 HU signifies osteoporosis. Clinical Case: A 60 year old female patient with history of endometrial cancer diagnosed at age of 57 and treated with hysterectomy and bilateral salpingo-oophorectomy, chemotherapy, then pelvic radiotherapy, was referred to endocrinology for pelvic insufficiency fractures evaluation. Two years after completing chemoradiotherapy, she complained of right groin and low back pain with difficulty walking. MRI pelvis showed bilateral sacral ala and right pubic ramus insufficiency fractures. She had normal serum mineral concentration, 25-OH vitamin D sufficiency, normal PTH, eGFR, liver function tests and 24-hour urine calcium excretion. Screening for celiac disease and multiple myeloma was negative. DXA scan BMD T-score showed osteoporosis, -3.0 at the right femoral neck. L1-L4 T-score was +0.4 but unreliable due to presence of degenerative changes. Four months after onset of pain, patient started romosozumab 210mg SQ monthly for a total of 12 doses, after which she started oral alendronate. Pain essentially resolved within 6 months of romosozumab therapy. C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were obtained at baseline, 3 and 12 months after romosozumab initiation. CTX was 362, 247 and 258 pg/mL (reference range, >49 years: not established), and P1NP was 82, 178 and 62 mcg/L (reference range, 20 - 108), respectively. Attenuation of L1 and L5 vertebral body was measured using CT abdomen and pelvis scans before and 5 months after radiotherapy, and before and after completion of romosozumab therapy. L1 attenuation measured 161, 132, 127 and 179 HU, and L5 measured 150, 46, 50 and 86 HU, respectively. Conclusion: Pelvic radiotherapy was associated with a decline in L1 CT attenuation and even greater magnitude of decrease at L5. Romosozumab was associated with clinical improvement, restoration of L1 CT attenuation and diminishment of regain at L5. Although L5 attenuation has not been previously assessed for osteoporosis, this site may be of predictive value in patients who receive pelvic radiotherapy.

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Bone Mineral Density Assessment Following Radiotherapy Related Insufficiency Fractures (RRIFs) of the Pelvis

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.494 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A243-A243

Author(s):

Victoria Chatzimavridou Grigoriadou ◽

Claire Emily Higham

Keyword(s):

Risk Factor ◽

Hip Fracture ◽

Fracture Risk ◽

Fragility Fracture ◽

Trabecular Bone Score ◽

Insufficiency Fractures ◽

Pelvic Radiotherapy ◽

Mineral Density ◽

T Score ◽

Radiotherapy Dose

Abstract Background: Pelvic radiotherapy causes symptomatic Radiotherapy Related Insufficiency Fractures (RRIFs) in around 20% of patients. Pathophysiology and predisposing factors for RRIFs are not well understood. Some studies have determined low BMD/osteoporosis to be a risk factor but only a few utilised DXA assessment of BMD at baseline prior to radiotherapy or at the time of RRIF development. Primary or secondary interventions to prevent/treat RRIFs have not been assessed. Methods: Retrospective analysis of patients (n=44; 42F; median age 65.5yrs [IQR 55, 73]) who underwent a DXA (Hologic) scan (Lumbar Spine (LS) (L1-4), Total Hip (TH), Femoral neck (FN) and Trabecular Bone Score (TBS)) following a diagnosis of pelvic RRIF between 2010–2019 at a tertiary referral cancer centre in the UK. Patient characteristics and treatment history were assessed. Osteoporosis (T-score <-2.5), osteopenia (T-score <-1 >-2.5) and normal BMD (T-score >-1) were defined as per WHO classification. Results: Cancer diagnoses; cervical (n=17), endometrial (n=9), vaginal (n=6), anal (n=6), other (n=6). Cancer treatments; chemotherapy (n=36), surgery (n=22), brachytherapy (n=26). Conventional risk factors for osteoporosis; previous fragility fracture (n=9, one on bisphosphonate prior to RRIF), smoking (n=7), glucocorticoid use (n=4), parental hip fracture (n=3), alcohol excess (n=3) and hypogonadism (n=2 and 8 on HRT). Median BMI = 25.4 [22.8, 28.5] kg/m2. Median interval between initiation of radiotherapy and RRIF was 9.8 [7.1, 19.3] months and between RRIF and DXA 3.5 [2, 8] months. At the time of the RRIF, 5 had normal BMD, 20 had osteopenia and 16 osteoporosis. Three patients were <40yrs at time of DXA (lowest Z-score -2 at LS in n=1). Median T-scores in LS, FN and TH were -1.8 [-2.8, -0.98], -1.65 [-2.4, -1.18] and -1.25 [-1.68, -0.5] respectively; N=24 had all Z-scores ≥-1. Median TBS T-score was -2.65 [-3.48, -2]. Median 10-yr hip fracture risk (FRAX HF) was 1.8% [0.7–4.1], major osteoporotic fracture risk (FRAX MO) was 8.9% [5.2- 13] (if RRIF included as FRAX risk factor: 2.9% [1–5] and 15% [8.7- 20] respectively). FRAX HF was ≥ 3% in n=14 and FRAX MO ≥ 20% in n=6 (accounting for RRIF: n= 20 and 12 respectively). Most patients therefore fell below the intervention threshold. Pelvic radiotherapy dose was negatively associated with LS BMD (p=0.0228). Body mass index was positively correlated with LS BMD (p=0.002). Discussion: Most patients did not have osteoporosis at the time of RRIF and overall had low fragility fracture risk as defined by FRAX. RRIFs can also occur with normal hip and spine BMD. Low BMD at the spine was however associated with higher pelvic radiotherapy dose. The mechanism of RRIFs is likely different to osteoporotic fragility fractures and whilst low BMD is a probable risk factor, further studies are required to fully understand their pathophysiology and how fracture risk should be best assessed in these patients.

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Bone mineral density and spongiosa architecture in correlation to vertebral body insufficiency fractures

Acta Radiologica ◽

10.1080/02841859809172221 ◽

1998 ◽

Vol 39 (5) ◽

pp. 538-542 ◽

Cited By ~ 7

Author(s):

R. Andresen ◽

S. Radmer ◽

D. Banzer

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Vertebral Body ◽

Unknown Etiology ◽

Insufficiency Fractures ◽

Mineral Density ◽

Group Iii ◽

Group I ◽

The Mean ◽

Group Ii

Objective: the clinical value of spinal quantitative CT (sQCT) and the structural patterns of the vertebral bone were studied Material and Methods: sQCT was performed on 246 patients with a mean age of 57 years for whom conventional lateral radiographies of the thoracic and lumbar spine were available. All patients were suffering from back pain of unknown etiology. the bone mineral density (BMD) of the midvertebral section of 3 lumbar vertebral bodies was determined by means of single-energy-(SE)-weighted QCT (85 kV). Spongiosa architecture and density profile analyses were made in the axial images. This was contrasted to BMD values ascertained in SE QCT. the mean BMD was compared to the number of fractures and the patients were divided into three groups: group I — no fracture; group II — one fracture; and group III 1 fracture Results: the mean BMD was: 134.3 (74.1–187.5) mg hydroxyapatite (HA)/ml in group I; 79.6 (58.6–114.3) mg HA/ml in group II; and 52.4 (13.1–79.1)mg HA/ml in group III. A significant deterioration in spongiosa structure was found with increasing demineralization: strongly rarefied patterns predominated in the fracture groups II and III Conclusion: sQCT provides a good risk assessment of the occurrence of vertebral body insufficiency fractures

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Vertebral body insufficiency fractures: detection of vertebrae at risk on standard CT images using texture analysis and machine learning

European Radiology ◽

10.1007/s00330-018-5846-8 ◽

2018 ◽

Vol 29 (5) ◽

pp. 2207-2217 ◽

Cited By ~ 11

Author(s):

Urs J. Muehlematter ◽

Manoj Mannil ◽

Anton S. Becker ◽

Kerstin N. Vokinger ◽

Tim Finkenstaedt ◽

...

Keyword(s):

Machine Learning ◽

At Risk ◽

Texture Analysis ◽

Vertebral Body ◽

Ct Images ◽

Insufficiency Fractures

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Sacral insufficiency fractures (SIF) following pelvic radiotherapy

Reports of Practical Oncology & Radiotherapy ◽

10.1016/j.rpor.2013.03.241 ◽

2013 ◽

Vol 18 ◽

pp. S234

Author(s):

E. Hortelano Pardo ◽

C. Carvajal Sanjines ◽

F. Casquero ◽

G. Iglesias ◽

B. Canteli ◽

...

Keyword(s):

Insufficiency Fractures ◽

Pelvic Radiotherapy ◽

Sacral Insufficiency Fractures

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Insufficiency fractures following pelvic radiotherapy of gynecologic malignancies

Turkish Journal of Oncology ◽

10.5505/tjoncol.2012.626 ◽

2012 ◽

Vol 27 (2) ◽

pp. 62-66

Keyword(s):

Insufficiency Fractures ◽

Pelvic Radiotherapy ◽

Gynecologic Malignancies

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The effect of aromatase inhibitors on bone mineral density measured by serial DXA scans

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.11065 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 11065-11065 ◽

Cited By ~ 1

Author(s):

K. J. Whannel ◽

J. C. Doughty ◽

C. R. Wilson ◽

A. McLellan

Keyword(s):

Bone Mineral Density ◽

Endocrine Therapy ◽

Bone Mineral ◽

Aromatase Inhibitors ◽

Fracture Rate ◽

Mineral Density ◽

First Line ◽

Dxa Scan ◽

T Score ◽

Dxa Scans

11065 Background: We are now using aromatase inhibitors (AI) in increasing numbers of women as treatment in the breast cancer care pathway. Studies have reported a loss of bone mineral density (BMD) with use of all AIs. It has been shown in our unit that 5 years of tamoxifen (T) in post-menopausal women prior to commencing an AI does not offer sufficient protection to prevent significant BMD loss when an AI is introduced, with 25% requiring concurrent bisphosphonate (BP) therapy. The aim of this study was to determine changes in serial DXA scan results over a 12month period in women taking AIs. Method: 62 women being considered for or in early stages of use of an AI attended for a DXA scan and re-scan at 12 months. Vertebral morphometry and fracture rate were assessed and risk factors for osteoporosis noted. Scan results were compared ( Table 1 ). Results: Mean age was 67yrs [standard deviation (SD) 9yrs]. The patients were grouped according to initial endocrine therapy. 13 (21%) switched from tamoxifen to arimidex after 2years, 3 (4.8%) switched from tamoxifen to exemestane after 3 years and 30 (48.4%) switched from tamoxifen to letrozole after 5 years. 11 (17.7%) had been on arimidex as first line endocrine therapy for <=2 years and 5 (8.1%) had been on letrozole as first line endocrine therapy for <=1 year. Mean t-score and SD was calculated at each site and results categorised by lowest t-score at any site. The overall decrease in BMD measured at 1.66% over the 12 months. Conclusion: We have demonstrated a decrease in BMD with AI treatment of 1.66% per year as well as an increase in fracture incidence and increased need for bisphosphonate therapy whilst on an AI. We would recommend that all patients on any AI receive annual DXA scans. [Table: see text] No significant financial relationships to disclose.

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Commentary: Bone Density in Women with Inflammatory Bowel Disease

Canadian Journal of Gastroenterology ◽

10.1155/2004/380703 ◽

2004 ◽

Vol 18 (3) ◽

pp. 183-184

Author(s):

A Hillary Steinhart

Keyword(s):

Inflammatory Bowel Disease ◽

Bone Density ◽

Bowel Disease ◽

Bone Growth ◽

Bone Size ◽

Growth Delay ◽

Mineral Density ◽

T Score ◽

Increased Risk ◽

Inflammatory Bowel

Conventional wisdom suggests that children who develop inflammatory bowel disease are at particularly increased risk of osteopenia and osteoporosis because of the effects of disease activity, nutritional factors and medications, especially glucocorticoids, during critical periods of bone growth. In this study, Bernstein et al endeavoured to determine the prevalence of reduced bone mineral density (BMD) in a population-based cohort of women with onset of inflammatory bowel disease (IBD) before 20 years of age. A secondary goal of the study was to compare estimates of the rates of osteopenia and osteoporosis using two different techniques: the more conventional areal BMD and volumetric BMD. The latter measure is designed to account for the reduction in bone size that can occur because of growth delay associated with childhood IBD. On the other hand, areal BMD is said to underestimate true bone density. The authors identified a cohort of patients using their research registry of IBD patients in Manitoba. Women who developed IBD before 20 years of age and who were younger than age 45 at the time of the study were invited to complete a questionnaire and undergo dual energy x-ray absorptiometry (DEXA). Of the 148 subjects who were approached, 70 were eligible and agreed to participate. More than 80% of the participating subjects had Crohn's disease (CD) and more than 80% affected had onset of disease after puberty. BMD did not appear to differ between the patients with prepubertal and those with postpubertal onset. Twenty-five of the 70 subjects had an areal T score less than -1 at one or more site. Only three had osteoporosis (T score less than -2.5). Individuals with a T score less than -1 had lower body weight and were more likely than other patients to have experienced amenorrhea in the year prior to DEXA testing. When T scores were adjusted for abnormalities in bone size, the mean volumetric T score was slightly but statistically significantly higher than the corresponding areal T score at each site.

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Comparison of Bone Mineral Density, T-Scores and Serum Zinc between Diabetic and Non Diabetic Postmenopausal Women with Osteoporosis

Journal of Laboratory Physicians ◽

10.4103/0974-2727.151681 ◽

2015 ◽

Vol 7 (01) ◽

pp. 043-048 ◽

Cited By ~ 7

Author(s):

Priyanka R Siddapur ◽

Anuradha B Patil ◽

Varsha S Borde

Keyword(s):

Bone Mineral Density ◽

Fracture Risk ◽

Postmenopausal Women ◽

Bone Mineral ◽

Mineral Density ◽

T Score ◽

Increased Risk ◽

Serum Zn ◽

Type 2 Diabetic

ABSTRACT Context: Postmenopausal osteoporosis is a public health problem. Diabetics are at increased risk of osteoporosis-related fractures. Zinc (Zn) has a role in collagen metabolism, and its levels are altered in diabetes. Aims: The aim was to compare bone mineral density (BMD), T-score and serum Zn between diabetic and nondiabetic postmenopausal women with osteoporosis to see if they influence increased fracture risk in diabetes. Settings and Design: It is a cross-sectional study conducted at Department of Biochemistry, Jawaharlal Nehru Medical College, Belgaum. Materials and Methods: Thirty type 2 diabetic and 30 age-matched (aged 45-75 years) nondiabetic Dual energy X-ray absorptiometry (DEXA) confirmed postmenopausal osteoporotics were included from January 2011 to March 2012. Serum Zn was analyzed by atomic absorption spectrophotometry. Statistical Analysis Used: Mean and standard deviation of the parameters of the two groups were computed and compared by unpaired Student's t-test. Relationship between variables was measured by Karl Pearson's correlation co-efficient. A statistical significance is set at 5% level of significance (P < 0.05). Results: T-score was significantly higher in diabetics compared with nondiabetics(−2.84 ± 0.42 vs. −3.22 ± 0.74) P < 0.05. BMD and serum Zn of diabetics showed a significant positive correlation with body mass index (BMI). Conclusions: Type 2 diabetic postmenopausal osteoporotics have a higher T-score than the nondiabetics. High BMI in type-2 diabetes mellitus (T2DM) may contribute to high BMD and may be a protective factor against zincuria. Increased fracture risk in T2DM could be due to other factors like poor bone quality due to hyperglycemia rather than BMD. Strict glycemic control is of paramount importance.

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Bone strength in multiple sclerosis: cortical midtibial speed-of-sound assessment

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1076oa ◽

2004 ◽

Vol 10 (5) ◽

pp. 488-493 ◽

Cited By ~ 4

Author(s):

Anat Achiron ◽

Shmuel Edelstein ◽

Y Ziev-Ner ◽

Uri Givon ◽

Zeev Rotstein ◽

...

Keyword(s):

Multiple Sclerosis ◽

Bone Strength ◽

Speed Of Sound ◽

Normal Population ◽

Ultrasound Measurement ◽

Score Distribution ◽

Population Norms ◽

Female Patients ◽

T Score ◽

Increased Risk

It has been previously suggested that multiple sclerosis (MS) patients are at increased risk for osteoporosis due to reduced mobility, decreased exposure to sunlight and recurrent steroid treatment. In order to systematically evaluate bone strength we assessed 256 MS patients (171 females, 75 males) through quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS, m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000 (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age- and gender-matched population norms. T-score distribution in male MS patients was similar to normal population. In contrast, for female MS patients T-score distribution was significantly different from population norms, reflected by increased SOS in 30.4% (T-score intervals 1- and-2 above normal values;P/0.001), compared with 7.4% in controls. These findings held true for both female patients younger and older than 45 years of age. Increased neurological disability and specifically motor involvement were more frequent in female patients with increased SOS (PB/0.05). Bone strength was preserved in MS patients. In a subgroup of female patients increased SOS was conceivably related to spasticity.

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