Introduction
Vertebral fracture (VF) is the most frequent manifesta tion of osteoporosis and may be symptomatic in 65-70% of cases 1,2. A prevalence of 10-24% has been reported 1, with 11.2% in Latin America 3. It is often diagnosed incidentally through a chest x-ray 1 and it occurs most often in T7-T8 and T11-T12 4. Identifying osteoporotic VFs allows secondary prevention of this disease, which prevents a new vertebral fracture 50-60% of the time 1,5. This study gathered clinical, sociodemographic and para-clinical information on patients with VFs at a tertiary care university hospital in Manizales, Colombia, over the last four years, in order to provide an appropriate characteriza tion of this population.
Materials and methods
This was a descriptive, observational cross-sectional study at SES Hospital Universitario de Caldas, which has a fracture coordination unit affiliated with the International Osteoporosis Foundation (IOF). Patients were identified who met the imaging criteria (by x-ray, nuclear magnetic resonance or tomography) for VF (≥25% vertebral height loss) associated with bone fragility, that is, low-energy fractures which occur after minimal trauma such as a fall from stand ing height or less, without tumors 6, who were admitted between January 2018 and January 2022. All patients with VFs were included.
The population's clinical and sociodemographic charac teristics were evaluated. The Charlson Comorbidity Index was classified as absent (0-1 point), low (2 points) and high (≥ 3 points) comorbidity 7; the Barthel Index was inter preted as total dependency (0-20 points), severe dependency (21-60), moderate dependency (61-90), slight dependency (91-99) and independence (100 points) 8); body mass index (BMI) was interpreted according to the WHO guidelines 9; the glomerular filtration rate was categorized according to the KDIGO guidelines 10; the hemoglobin level was classified as normal, or mild, moderate or severe anemia, according to the WHO criteria 11; inadequate consumption of dairy products was defined as less than two servings per day, according to the dietary guidelines based on foods for the Colombian population over the age of two published by the Ministry of Health and Instituto Colombiano de Bienestar Familiar [Colombian Institute for Family Wellbeing] 12; low albumin was defined as <3.5 and normal as ≥3.5 13; serum calcium levels were normal between 8.5 and 10.2, low at <8.5 and high at ≥10.3 14; phosphorus was consid ered normal in a range from 3.4-4.5 mg/dL 15; TSH from 0.3-5.5 mIU/L 16; PTH 15-68.3 pg/mL 17 and alkaline phosphatase 20-140 U/L 18. Furthermore, vitamin D was classified as severe deficiency (<10 ng/mL), mild deficiency (10-20 ng/mL), insufficiency (20-30 ng/mL) and normal (> 30 ng/mL) 19; testosterone was considered normal between 2.1-9.7 ng/mL 20 and, finally, the fracture grade was categorized according to the Genant classification 21.
A descriptive statistical analysis was performed with Stata version 16.1 (StataCorp, TX, USA). Continuous variables with a normal distribution according to the Kolmogorov-Smirnov test are described using averages, standard de viation (SD) and 95% confidence intervals; continuous variables with a non-normal distribution are described using medians and interquartile range. Categorical variables are described in frequency distribution tables.
Results
A total of 174 patients were included, accounting for 100% of the sample with VFs. The average age was 77.7 years, with an SD of 9.2, 68.2% of whom were women. Altogether, 89.4% of the patients had a high Charlson Comorbidity Index and 61.7% showed complete independence on the Barthel index. Tobacco and alcohol exposure risk factors were analyzed, finding that most did not use them. Regarding their nutritional status, 54.6% of the analyzed sample had malnutrition (whether overweight, underweight or obesity). Prior dairy product consumption was inadequate in most patients and 60.1% had polypharmacy. Kidney function was adequate, with 52.5% having a GFR greater than 90 ml/min/1.73 m2 according to the Cockroft-Gault equation (Table 1).
n % | ||
---|---|---|
Age (years) | ||
Average | 77.7 | |
SD | 9.2 | |
95%CI | 76.3 - 79.1 | |
Sex | ||
Female | 118 | 68.2 |
Male | 55 | 31.8 |
Charlson Comorbidity Index | ||
High | 117 | 89.4 |
Low | 15 | 10.6 |
Barthel Index | ||
Severe dependency | 4 | 2.5 |
Moderate dependency | 11 | 6.9 |
Slight dependency | 46 | 28.9 |
Complete independence | 98 | 61.7 |
Smoking | ||
Active smoker | 9 | 6.6 |
Mild ex-smoker | 5 | 3.6 |
Moderate ex-smoker | 3 | 2.2 |
Heavy ex-smoker | 23 | 16.8 |
No | 97 | 70.8 |
Alcohol | ||
Yes | 6 | 4.2 |
No | 136 | 95.8 |
Body mass index (BMI) | ||
Low weight | 8 | 5.6 |
Normal | 64 | 45.4 |
Overweight | 45 | 31.9 |
Obesity I | 19 | 13.5 |
Obesity II | 5 | 3.6 |
Glomerular filtration rate (Cockroft-Gault) | ||
Normal (G1) | 91 | 53.5 |
Mild reduction (G2) | 54 | 31.7 |
Mild to moderate reduction (G3a) | 12 | 7.1 |
Moderate to severe reduction (G3b) | 7 | 4.1 |
Severe reduction (G4) | 3 | 1.8 |
Kidney failure (G5) | 3 | 1.8 |
Polypharmacy | ||
Yes | 89 | 60.1 |
No | 59 | 39.9 |
Dairy product intake | ||
Adequate | 21 | 14.6 |
Inadequate | 123 | 85.4 |
SD: standard deviation. | 95%CI: 95% confidence interval. |
Among the clinical characteristics of the fractures, 51.4% had severe fractures (≥40% vertebral body height loss ac cording to Genant) 21. Regarding the number of fractures, 56.6% had a single fracture, while 6.2% had ≥4 fractures, with an unknown mechanism, equivalent to 80.7% of the pa tients having prevalent fractures. Notably, 19.8% had already had a prior fracture and 15.1% were already on medications for osteoporosis, 4.6% of whom were mainly managed with oral bisphosphonates. Of the analyzed sample, 2.9% had a fatal outcome due to complications of comorbidities other than osteoporosis (Table 2).
n % | ||
---|---|---|
Fracture grade | ||
Mild | 13 | 17.5 |
Moderate | 23 | 31.1 |
Severe | 38 | 51.4 |
Number of fractures | ||
1 | 73 | 56.6 |
2-3 | 48 | 37.2 |
≥4 | 8 | 6.2 |
Fracture mechanism | ||
Unknown | 138 | 80.7 |
Slipping | 15 | 8.8 |
Instability | 11 | 6.4 |
Tripping | 5 | 2.9 |
Syncope | 1 | 0.6 |
Physical effort | 1 | 0.6 |
Prior fractures | ||
Spinal column | 9 | 5.8 |
Hip | 6 | 3.9 |
Humerus | 5 | 3.3 |
Ulna/radius | 8 | 5.2 |
Tibia | 1 | 0.8 |
Spinal column, humerus and radius | 1 | 0.8 |
None | 122 | 80.2 |
Type of treatment | ||
Conservative treatment | 128 | 84.7 |
Vertebroplasty | 20 | 13.2 |
Osteosynthesis | 2 | 1.3 |
Laminectomy | 1 | 0.8 |
Previous treatment | ||
Oral bisphosphonate | 7 | 4.6 |
Zoledronic acid | 5 | 3.2 |
Denosumab | 5 | 3.2 |
Teriparatide | 5 | 3.2 |
Combined | 1 | 0.6 |
None | 129 | 84.9 |
Calcium and vitamin D supplementation therapy | ||
Yes | 32 | 21.1 |
No | 120 | 78.9 |
Vital status at discharge | ||
Alive | 166 | 97.1 |
Deceased | 5 | 2.9 |
An evaluation of the paraclinical profile showed that most of the patients had an adequate hemoglobin level, with an average of 12.9 g/dL and an SD of 2.1. Albumin and vitamin D were low, with the latter mostly in the mild deficiency range. The only elevated laboratory test was PTH. Most of the analyzed sample had normal phosphorous, calcium and alkaline phosphatase levels (Table 3).
N s | ||
Hemoglobin | ||
Average | 12.9 | |
SD | 2.1 | |
95%CI | 12.6 - 13.2 | |
Hemoglobin level | ||
Normal Mild anemia Moderate anemia Severe anemia | 141 | 83.4 |
17 | 10.1 | |
9 | 5.3 | |
2 | 1.2 | |
Creatinine | ||
Median | 0.8 | |
IQR | 0.7 - 1.0 | |
Albumin | ||
Average | 3.3 | |
SD | 0.5 | |
95%CI | 3.2 - 3.4 | |
Albumin level | ||
≤3.5 | 94 | 59.5 |
>3.5 | 64 | 40.5 |
Calcium | ||
Average | 9.3 | |
SD | 5.7 | |
95%CI | 8.4 - 10.2 | |
Calcium level | ||
Normal | 122 | 74.8 |
Low | 37 | 22.7 |
High | 4 | 2.5 |
Phosphorus | ||
Average | 3.75 | |
SD | 1.5 | |
95%CI | 3.5 - 4.0 | |
Phosphorus level | ||
Normal | 96 | 67.6 |
Low | 25 | 17.6 |
High | 21 | 14.8 |
TSH | ||
Average | 3.67 | |
SD | 4.97 | |
95%CI | 2.89 - 4.44 | |
TSH level | ||
Normal | 117 | 73.1 |
Low | 10 | 6.3 |
High | 33 | 20.6 |
Parathyroid hormone | ||
Average | 70.06 | |
SD | 56.13 | |
95%CI | 61.18 - 78.94 | |
Parathyroid hormone level | ||
Normal | 74 | 47.4 |
Low | 0 | 0.0 |
High | 82 | 52.6 |
Alkaline phosphatase | ||
Average | 91.2 | |
SD | 45.6 | |
95%CI | 81.9 - 100.5 | |
Alkaline phosphatase level | ||
Normal | 82 | 85.4 |
High | 14 | 14.6 |
Vitamin D | ||
Average | 21.6 | |
SD | 10.8 | |
95%CI | 19.8 - 23.3 | |
Vitamin D level | ||
Normal | 28 | 18.7 |
Insufficiency | 37 | 24.7 |
Mild deficiency | 69 | 46.0 |
Severe deficiency | 16 | 10.6 |
Testosterone | ||
Average | 2.98 | |
SD | 1.96 | |
95%CI | 2.26 - 3.70 | |
Testosterone level | ||
<2.62 | 14 | 45.1 |
>2.62 | 17 | 54.9 |
SD: standard deviation 95%CI: 95% confidence interval IQR: interquartile range |
Discussion
Our findings suggest that, when osteoporotic VFs occur, most are in malnourished female patients with low vitamin D and high PTH. Eighty percent of the cases were prevalent VFs (asymptomatic).
The World Health Organization (WHO) has defined osteoporosis as a metabolic disease characterized by low bone mass and deteriorated bone microarchitecture leading to greater fragility and, consequently, an increased risk of fracture. Bone mineral density (BMD) assessment through a bone density scan is the gold standard for diagnosing os teoporosis, as it detects a reduction equal to or greater than -2.5 standard deviations (SD) compared to the mean value obtained for young people of the same sex 22,23. However, diagnosing osteoporosis based exclusively on the BMD scores identifies less than 50% of the people who end up having an osteoporotic fracture 23, and a diagnosis based on a history of a vertebral or hip fragility fracture is also accepted 24. According to the International Osteoporosis Foundation (IOF), osteoporotic fractures affect one out of three women and one out of five men 50 years old or older. This is why it is important to identify other characteristics that could suggest an osteoporotic substrate, as shown in this study.
To understand the pathophysiology and focus the treat ment of osteoporosis, the functions of PTH and vitamin D must be understood correctly, along with their relationship in maintaining calcium homeostasis.
Calcium-sensing receptors (CaSR) in the parathyroid glands regulate the secretion of PTH, increasing its pro duction when calcium levels decrease 25. Parathyroid hormone stimulates bone resorption, calcium absorption in the duodenum, and tubular reabsorption of calcium 26 as well as 1,25-dihydroxy-vitamin D synthesis in the kidney which, in turn, increases calcium reabsorption in the gut and kidney 27,28. In the osteoblasts, it stimulates the RANKL-RANK system, which fosters osteoclast differentiation and survival 26. Therefore, both hyperparathyroidism and vitamin D deficit are predisposing factors for osteoporosis. They were both abnormal in this study, in line with what is described in the literature.
It has been scientifically shown that serum PTH levels rise in a compensatory fashion when vitamin D levels and/ or calcium intake decrease. A physiological increase has also been associated with older age 29, findings which were also seen in this study.
Specifically regarding VFs, they are reported to be the most common complication of osteoporosis 30 and, ac cording to IOF, are one of the main causes of pain, disability, loss of physical independence and premature death in mil lions of people around the world. An isolated VF tends to be the first osteoporotic fracture to occur, and precedes the onset of proximal femoral, radial, sacral or pelvic osteopo rotic fractures 31-33, which has been termed the "cascade effect" 33-35, with a five times greater risk of a new VF after the first one, and a 2-3 times greater risk of a hip frac ture 36,37. In this regard, recognizing osteoporotic VFs and providing appropriate treatment may prevent or delay the occurrence of a subsequent fracture.
A study on the global incidence and prevalence of osteoporotic VFs found that at least one of every five men and women over the age of 50 have one or more vertebral fractures 37. The European Vertebral Osteoporosis Study (EVOS) 38, the European Prospective Osteoporosis Study (EPOS) 39 and the LAVOS study 3 showed a 12.2% prevalence of osteoporotic VFs in both men and women, with an incidence of 10.7% in women and 5.7% in men, in European patients over the age of 50. Another recent global study also reported 20-24% prevalence rates in white North American women ≥50 years old, with a white/black ratio of 1.6, determining that the prevalence of these is lower in Latin America than in Europe and North America (11-19%), possibly due to poor reporting 37.
A study in Colombia which collected information from 10 fragility fracture healthcare facilities in four cities and obtained 1,699 patient charts found an average age in both men and women of 79 years, with more women than men 40, findings which are congruent with this study. In addition, they reported diabetes mellitus, vitamin D insuf ficiency and corticosteroid therapy 40 as some of the most frequent secondary causes of osteoporosis, with vitamin D insufficiency also seen as a cause in our study, in line with these findings.
There are many modalities for diagnosing VFs. X-rays have been the most frequent diagnostic method, with the Genant method being the standard for evaluating images 2,21,34, describing four grades: grade 0 indicates no fracture, grade 1 indicates a 20-25% height loss, grade 2 a 25-40% loss and grade 3 indicates a more than 40% loss 1.
On the other hand, magnetic resonance imaging has greater sensitivity for diagnosing VFs than other imaging techniques and can help determine the age of the fracture, as well as distinguish osteoporotic changes from neoplastic fractures 31,36. Given its cost in our setting, it is not recommended for routine use.
Up to 65% of osteoporotic VFs are asymptomatic 1,2,5 and they should be suspected with height losses of at least 4 cm, with pain being the most common clinical manifestation in those who develop any symptom 32,41. They can cause decreased activity and physical function, with social isola tion and work limitations 31,42. They tend to go unnoticed or have their symptoms attributed to other common etiolo gies like degenerative joint disease or muscle pain 24,33.
A study evaluating 70 patients with fragility fractures found that 81.43% of them reported having been examined by a physician in the year prior to the fracture; at least 65% of the patients in the study population met the criteria for osteoporosis screening, but only 11.4% had been screened. In addition, they showed a post-fragility fracture survival probability of close to 70% for hospital stays lasting 30 or more days, increasing to 94% if discharged at 15 days, concluding that both primary and secondary prevention in our setting has been insufficient 43. The most frequent diagnosis in our setting is made incidentally through a chest x-ray, and therefore only approximately 40 to 60% of osteoporotic VFs are diagnosed 11,35, with only 40% of these women and less than 20% of the men referred for osteoporosis assessment 11,35.
In hospitalized patients, it has been suggested that caring for VFs detected despite not being the reason for hospital ization was a more effective secondary fracture prevention strategy than ambulatory treatment deferred until after discharge 36. Therefore, it has also been recommended that radiologists report the VFs identified on other x-rays, such as chest x-rays, regardless of the reason for ordering the test, and that, with this report, timely assessment and treatment be started 2,44. In our study, this strategy was applied during recruitment and follow up of patients in the Coordinated Fracture Program at SES Hospital Uni versitario de Caldas. Notably, early diagnosis and prompt treatment can lead to an up to 41% reduction in the risk and recurrence of osteoporotic fractures, thus helping decrease morbidity and mortality and their resulting costs 43.
A spine x-ray should be ordered for patients complaining of thoracolumbar pain; however, given its multiple causes, this should be individualized to the patient, evaluating clinical markers, the physical exam and risk factors for osteoporosis 2. Some characteristics that may suggest the presence of a VF are advanced age, female sex, lateral waist pain, back pain which improves with lying down or is described as "crushing" and not radiating to the lower extremities, the presence of smoking, a history of COPD, previous fractures, late menarche, the chronic use of ste roids and a 4 cm loss of height 45.
There are diverse consequences of osteoporotic VFs: short or long-term physical, psychological, social and public health problems 11,31. In addition, they indicate a significantly greater risk of developing new fractures in the future and are also associated with greater morbidity and mortality 6,11,45, contributing to other systemic complications like reduced pulmonary function and gastrointestinal problems including hiatal hernia, gastroesophageal reflux, constipation and intestinal obstruction 37; thus, identifying and treating them early could decrease future morbidity.
Study weaknesses
Most of the diagnostic imaging reports by radiology did not describe the severity according to the grade of the fracture. In addition, a small percentage of patients did not have some of the data, as shown in the results.
Conclusions
Vertebral fracture is the most common fracture in people with osteoporosis and tends to be the first to occur. There fore, its timely identification and treatment helps prevent new osteoporotic fractures, both in the vertebrae as well as the long bones. This study provided, for the first time, the clinical, paraclinical and sociodemographic characterization of patients in a Colombian population, in order to facilitate early intervention, improving their prognosis and morbidity. These characteristics included age over 78 years, female sex, vitamin D deficit, elevated PTH, malnutrition according to BMI or albumin levels, inadequate dairy product consump tion and a multiple disease profile.