Analysis of Bone Density Among Patients with Urolithiasis: The Role of Hypercalciuria in Bone Loss

ABSTRACT

INTRODUCTION: A kidney stone is a common urologic complaint. The association between hypercalciuria and bone mineral density (BMD) is well known. However, BMD reduction is also recognized among normocalciuric patients.

OBJECTIVE: Bone density in patients with stones was analyzed for the variables of age, sex, and stone configuration. Data were compared with a control group.

METHODS: Participants were 340 randomly chosen patients with upper urinary calcium stones. The control group included 340 healthy participants who were age and sex matched with the patient group. The quantitative variables included age, body mass index, T-score of bone densitometry in the lumbar vertebrae (L2-L4) and femoral neck, and the serum levels of uric acid, calcium, potassium, sodium, phosphor, alkaline phosphatase and parathyroid hormone. Furthermore, each patientâ€™s 24-hour urine was studied for levels of creatinine, oxalate citrate, uric acid calcium, urea, and total volume.

RESULTS: The mean age of the patients was 43.22 years (SD =12.62); mean body mass index (BMI) was 27.44 kg/m2 (SD = 6.16). Lumbar vertebral bone densitometry bone mineral density (BMD) was normal in 144 patients (42.4%) and low normal in an additional 20 patients. One hundred forty patients (41.2%) had osteopenia and 56 (16.5%) were osteoporetic. Femoral neck BMD was normal in 188 patients (55.3%) and low normal in 28 patients. In comparison with the control group, lumbar and femoral BMD were significantly lower in patients with renal stones (P < .05). There were no significant differences among groups in quantitative variables, with the exception of serum uric acid level. There was a significant correlation between both lumbar T-score and femoral neck T-score with 24 hour urine uric acid. Lumbar T-scores increased in inverse relationship with age (P = .03).

CONCLUSION: The authors established that patients who form renal stones have a reduction in bone density. There was no significant difference in bone loss between hypercalciuric and normocalciuric patients, which indicates the existence of some interfering factors other than increased calcium loss. A low-calcium diet does not decrease stone formation, and it also leads to calcium imbalance and bone loss. Considering that the role of hypercalciuria in bone loss was not proven in this study and considering that a low-calcium diet has no proven role in renal stone prevention, the authors do not suggest low-calcium diets for renal stone formers.

KEYWORDS: Bone mineral density; Urolithiasis; Low-calcium diet; Hypercalciuria

CORRESPONDENCE: Dr. Mahmood Molaei, Department of Urology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran ()

INTRODUCTION

A kidney stone is a common urologic complaint, affecting approximately 10% of the global population. The most common types of renal calculi are calcium stones, with calcium oxalate stones the most common subtype [1]. According to numerous studies, 90% of people who form calcium stones have a metabolic disorder that influences bone metabolism and leads to reduction of bone density and osteoporosis [2,3]. Therefore, it is important to analyze the patientâ€™s bone density.

Based on several studies, over 60% of patients who form idiopathic calcium renal stones have hypercalciuria [4]. The association between hypercalciuria and bone mineral density (BMD) is well recognized and calcium loss and low-calcium diet are considered the cause of calcium alterations [5,6,7]. However, BMD reduction is also recognized among normocalciuric patients [8], indicating the existence of other interfering factors. The other factors may include bone absorption by means of prostaglandins, occult metabolic acidosis, and 1,25-(OH)2-vitamin D3 disorders [4].

The purpose of the present investigation was to study bone density in patients with urinary stones and a control group. The variables included age, sex, and stone configuration.

METHODS

Participants

The participants for this prospective study were 340 outpatients from the urology clinic. All had documented upper urinary calcium stones, known through stone analysis. They were referred to the clinic over a period of 2 years. None of the patients had essential hyperparathyroidism, medullary sponge kidney, renal tubular acidosis, sarcoidosis, neoplasm, immobilization, urinary tract infection, or renal failure. Additionally, none of the patients consumed steroids, calcium, thyroxin, H2blocker, anticonvulsants, vitamin C, heparin, vitamin D, diuretics, estrogens, fluoride, or biphosphonates.

The control group had 340 participants who were age and sex matched with the patient group. These individuals had no history of stone formation or potential causes of osteopenia (eg, chronic disease, hyperparathyroidism, hyperthyroidism, gastrointestinal disease, prolonged immobilization, or prolonged corticosteroid therapy).

Procedures

The investigation was approved by the local ethical committee. All participants provided informed consent.

Bone densitometry was performed by dual-energy X-ray absorbiometry (DXA) technique. Bone density was measured in the lumbar vertebrae (L2-L4) and femoral neck and reported in mg/cm3. Furthermore, each patientâ€™s 24-hour urine was studied for levels of creatinine, oxalate, citrate, uric acid calcium, urea, and total volume.

The measured variables included age, height, weight, body mass index (BMI), T scores of bone densitometry in the lumbar vertebrae (L2-L4) and femoral neck, and the serum levels of uric acid, calcium, potassium, sodium, phosphor, alkaline phosphatase and parathyroid hormone (parathormone). T-score is the standard deviation below the average for a young adult at peak bone density. Based on BMD results, patients fell into 3 categories: normal, osteopenic and osteoporetic.

SPSS software (version 15) was used for statistical analysis. A descriptive analysis provided frequencies, central tendency, and dispersion measures. The Pearson product moment correlation was performed for compared variables. The Student t test was used to compare quantitative variables among patients in the 3 categories (normal, osteopenic, osteoporetic). In all cases, a P value < .05 was considered significant.

RESULTS

The authors studied 340 patients, including 224 men (65.9%) and 116 women (34.1%). Their mean age was 43.22 years (SD = 12.62) and their mean (BMI) was 27.44 kg/m2 (SD = 6.16). The mean age of the control group was 40.15 years (SD = 16.62) and their BMI was 24.44 (SD = 8.27). The chemical analysis of the patientsâ€™ stones showed pure calcium oxalate (n = 220), pure calcium phosphate (n = 56) and a combination of several ions (n = 64).

Serum Levels

Table 1 contains means and standard deviations for all serum levels (serum uric acid, potassium, calcium, sodium, urea, creatinine, phosphorus, alkaline phosphatase, parathyroid hormone) and 24-hour urine levels (creatinine, urea, oxalate, citrate, calcium and total volume) for each group. Results of t tests showed that there were no significant group differences in any measures except in serum uric acid level. The serum uric acid level was significantly higher for patients with osteoporosis (t_inf = 1.96, P = .025).

Bone Mineral Density

Table 2 contains the lumbar vertebral densitometry levels of male and female patients. Results of a t test revealed no statistically significant differences in lumbar vertebral densitometry levels between males and females.

Table 3 contains the femoral neck densitometry levels of male and female patients. Results of a t test revealed no statistically significant differences in femoral neck densitometry levels between males and females.

The majority of patients had BMD that was normal or osteopenic using lumbar vertebral or femoral vertebral densitometry tests. Lumbar vertebral BMD was normal in 144 patients (42.4%) and low normal in an additional 20 patients. Femoral vertebral BMD was normal in 188 patients (55.3%) and low normal in 28 patients.

The lumbar vertebral BMD of the control group showed that 104 participants (30.6%) were osteopenic, 28 (8.2%) were osteoporetic, and 208 had normal BMD. The femoral vertebral BMD of the control group showed 72 participants (21.2%) were osteopenic and 4 (1.2%) were osteoporetic.

Table 4 and Table 5 show the lumbar and femoral vertebral densitometry BMD results for patients with renal stone configuration. Results of the t test showed that lumbar and femoral BMD was significantly lower in patients with renal stones (t_inf = 2.57, P=.005). There were no statistically significant differences in stone configuration among patients in the 3 groups (normal, osteopenic and osteoporetic).

Lumbar vertebral osteoporosis was reported in 16.3% of normocalciuric patients and 20% of hypercalciuric patients. Results of the t test showed no significant differences in the lumbar or femoral vertebral BMD values of the normocalciuric and hypercalciuric patients.

Correlation Between Serum Levels and Bone Mineral Density

Table 6 contains the probability values of Pearson correlations between femoral neck and lumber vertebral T-scores and 24-hour urine levels of oxalate, citrate, uric acid and calcium. The correlation between T-scores and age is also presented. There was a significant correlation between both lumbar T-score (Pearson r = .22; P = .03) and femoral neck T-score (Pearson r = .22; P = .04) and 24 hour urine uric acid. Lumbar T-scores increased in inverse relationship to age. In other words, an increase in age led to a decrease in T-score. There were no other significant correlations between T-score and the other variables. BMD reduction among menopausal women was obviously significant (t_inf = 2.33, P = .01).

A power analysis was not calculated. Therefore, there is a possibility that some of the statistical comparisons showed statistically significant differences due to chance.

DISCUSSION

Renal stone development is a multifactorial disease. The diet of a patient with renal stones has a direct impact on urine composition [9,10]. Therefore, it has been hypothesized that a change from inappropriate habitual diet patterns might be the key to treating renal stones.

During the past decade, incidence of renal stone formation has increased among adults and children, which emphasized the importance of an appropriate diet [11]. Low calcium intake is one of the main causes of alteration in healthy bone formation. The current data suggest that adequate calcium intake through milk or milk products in childhood and adolescence is highly necessary for achieving maximum bone mass (peak adult bone mass) and preventing osteoporosis [12].

Bone mineral density is defined as the function of bone size that increases during growth. BMD is increased by maturation and reaches its maximum at the age of puberty [13]. BMD increase is associated with factors such as weight, height, prepubertal growth, and BMI. Weight is a leading factor for females at the age of puberty [14]. Vertebral cortical density increases with aging [13]. Calcium plays an essential role in bone health during the life cycle, which has its highest impact around the age of puberty [15].

In the present study, the authors found that patients with renal stones had a reduction of bone density in comparison with a control group. This reduction was noticed even in normocalciuric patients. There was no significant difference in bone loss between hypercalciuric and normocalciuric patients, which indicates the existence of some interfering factors other than increased calcium loss. Parathyroid hormone was normal among all patients, so this hormone is not considered a cause of bone loss. Thus, the question still remains as to whether hypercalciuria is a cause or consequence of bone loss.

Patients with calcium stones are at a higher risk of bone disorders due to a low-calcium diet, and they could prevent these disorders by adequate calcium intake [16,17]. Patients with BMD reduction usually have a long history of stone formation, which proves that this process is silent and progressive. A low-calcium diet does not decrease stone formation and it leads to calcium imbalance and bone loss [18,19]. Considering that the role of hypercalciuria in bone loss was not proven in this study and considering that a low-calcium diet has no proven role in renal stone prevention, the authors do not suggest low-calcium diets for renal stone formers. However, more multifactorial studies are needed before concluding that a low-calcium diet would not be beneficial.

One group at high risk for renal stones and osteopenia are menopausal women with urolithiasis [20]. Therefore, appropriate osteopenia and stone treatment should be considered for them.

Bone density was associated with renal function factors (eg, urinary sodium, pH, and uric acid), indicating that osteopenia was not just associated with calcium metabolism [15]. In the present study, lumbar vertebral osteopenic patients showed a significantly higher level of uric acid in comparison with normal and osteopenic groups. More research is needed to understand the role of uric acid in bone density.

REFERENCES

Anderson RA. A complementary approach to urolithiasis prevention. World J Urol. 2002;20(5):294-301.

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