Acute Alteration in Bone Mineral Density and Biochemical Markers for Bone Metabolism in Nephrotic Patients Receiving High-Dose Glucocorticoid and One-Cycle Etidronate Therapy

Abstract

It is widely known that glucocorticoids induce and accelerate osteoporosis. High-dose glucocorticoids are administrated daily to patients in the acute phase of nephrotic syndrome. It could be inferred that high-dose glucocorticoids rapidly decrease patients' basal bone mineral density (BMD) and this accelerates the natural progress of osteoporosis associated with aging or menopause. Nine nephrotic patients (male/female: 5/4) without previous prednisolone administration were chosen to measure BMD and the level of the markers for bone turnover before and after treatment for 3 months (total prednisolone administration: 4.5 +/- 0.0 g). Twenty-three patients under remission with prednisolone administration (male/female: 14/9) were included in the long-term treatment group. Patients in this group whose %YAM in the lateral lumbar spine was less than 89% were classified into a low BMD group (n = 10, male/female: 3/7). They were administered etidronate disodium at 200 mg/day for 14 days. BMD and % of young adult mean (YAM) in the lumbar spine (L2-L4 in lateral objection) and other regions were measured by dual-energy X-ray absorptiometry. As markers of bone metabolism, the urinary level of deoxypyridinoline (Dpd) was determined to evaluate osteogenesis, and serum osteocalcin was measured to evaluate bone resorption. BMD of the lumbar spine significantly decreased in the 3-month treatment group (752 +/- 96 mg/cm(2), 7 +/- 4% reduction) compared with the pretreatment group (810 +/- 85 mg/cm(2)). BMD in the long-term treatment group decreased continuously (683 +/- 135 mg/cm(2)). No significant differences were noted in other measurement sites. BMD in the etidronate treatment group increased significantly (597 +/- 55 mg/cm(2)) compared with the pretreatment group (549 +/- 76 mg/cm(2)). Etidronate did not change BMD at the sites with a normal BMD. Among the biochemical markers (BM) examined, the urinary level of Dpd (nMol/liter. Cr) significantly increased in the 3-month treatment group (8.6 +/- 5.1 nMol/liter.Cr) compared with the pretreatment group (5.8 +/- 2.0 nMol/liter. Cr). No significant differences were seen in the BMs measured in the long-term treatment group. The urinary Dpd level of the etidronate treatment group decreased (3.9 +/- 1.4 nMol/liter. Cr) compared with the pretreatment group. These data indicate that etidronate could improve the accelerated bone resorption. In conclusion, high-dose glucocorticoid therapy causes rapid bone resorption and accelerates the natural progress of osteoporosis associated with aging or menopause. Etidronate administration prevents the progress of osteoporosis in nephrotic patients. Preventive treatment should be performed when the estimated BMD in 3 months falls below the baseline by more than 7 +/- 4%, reaching the therapeutic range.

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

“…After a median of 18 days following GC initiation, every 1 mg/m 2 increase in GC therapy (prednisone equivalents) was associated with a decrease in spine BMD Z-score of almost 0.4 standard deviation (SD). This finding was consistent with a recent report in adult GC-treated NS in which significant declines in spine BMD Z-scores were evident after just 12 weeks of GC therapy [10]. Similarly, a large cross-sectional case-control study showed lower spine bone mineral content after 4 years of GC exposure in children with steroid-sensitive NS, suggesting the potential for residual bone mass deficits in the longer term [11].…”

“…A number of studies have shown a significant decrease in LS BMD Z-scores in the first few weeks of GC therapy, both in children [36] and in adults [10] with NS. These observations are attributable to the acute effects of GC on bone, as demonstrated in animal models [37], and on trans-iliac bone specimens from adults [38].…”

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome

“…First, it is well-known that GCs have a predilection for interference with trabecular bone architecture, both in humans [6] and in animal models [5]. Furthermore, bone resorption markers increase acutely in adults with NS following administration of GCs [28], and are associated with a significant decline in spine BMD after a few weeks of therapy in both adults [28] and children with NS [9]. In addition, spine BMD has been shown to decline rapidly in adults following GC initiation for organ transplantation [29].…”

The Epidemiology of Corticosteroid-Induced Osteoporosis: a Meta-analysis

“…Figure 4 shows the bone loss from the spine of first-time user followed in longitudinal studies [9,20,25,33,38,42,51,56,67,71]. One limitation of evaluating bone loss longitudinally is that daily dose may vary and reduce over time.…”