M. Nobile

Alendronate Prevents Further Bone Loss in Renal Transplant Recipients

The aim of this study was to investigate the effects of alendronate, calcitriol, and calcium in bone loss after kidney transplantation. We enrolled 40 patients (27 men and 13 women, aged 44.2 ± 11.6 years) who had received renal allograft at least 6 months before (time since transplant, 61.2 ± 44.6 months). At baseline, parathyroid hormone (PTH) was elevated in 53% of the patients and the Z scores for bone alkaline phosphatase (b‐ALP) and urinary type I collagen cross‐linked N‐telopeptide (u‐NTX) were higher than expected (p < 0.001). T scores for the lumbar spine (−2.4 ± 1.0), total femur (−2.0 ± 0.7), and femoral neck (−2.2 ± 0.6) were reduced (p < 0.001). After the first observation, patients were advised to adhere to a diet containing 980 mg of calcium daily and their clinical, biochemical, and densitometric parameters were reassessed 1 year later. During this period, bone density decreased at the spine (−2.6 ± 5.7%; p < 0.01), total femur (−1.4 ± 4.2%; p < 0.05), and femoral neck (−2.0 ± 3.0%; p < 0.001). Then, the patients were randomized into two groups: (1) group A—10 mg/day of alendronate, 0.50 μg/day of calcitriol, and 500 mg/day of calcium carbonate; and (2) group B—0.50 μg/day of calcitriol and 500 mg/day of calcium carbonate. A further metabolic and densitometric reevaluation was performed after the 12‐month treatment period. At the randomization time, group A and group B patients did not differ as to the main demographic and clinical variables. After treatment, bone turnover markers showed a nonsignificant fall in group B patients, while both b‐ALP and u‐NTX decreased significantly in alendronate‐treated patients. Bone density of the spine (+5.0 ± 4.4%), femoral neck (+4.5 ± 4.9%), and total femur (+3.9 ± 2.8%) increased significantly only in the alendronate‐treated patients. However, no trend toward further bone loss was noticed in calcitriol and calcium only treated subjects. No drug‐related major adverse effect was recorded in the two groups. We conclude that renal transplanted patients continue to loose bone even in the long‐term after the graft. Alendronate normalizes bone turnover and increases bone density. The association of calcitriol to this therapy seems to be advantageous for better controlling the complex abnormalities of skeletal metabolism encountered in these subjects.

Effects of one-year cyclical treatment with clodronate on postmenopausal bone loss.

We studied 60 women with postmenopausal bone loss randomly allocated to the following treatments: Group 1 (20 patients), no treatment; Group 2 (20 patients), clodronate 400 mg daily by mouth for 30 consecutive days, followed by 60 days of no treatment; Group 3 (20 patients) oral calcitriol 2 mcg by mouth for 5 days and oral clodronate 400 mg daily for additional 25 days, followed by 60 days of no treatment. The therapeutic cycles were repeated four times in the 12-month study period. In the 36 treated patients of Groups 2 and 3 who completed the study period we observed a progressive and significant increase in lumbar bone density both at 6 and 12 months of therapy, without significant differences between the two treatment protocols (+3.88 +/- 0.65%, P < 0.001 and +3.21 +/- 0.89%, P < 0.005 in Groups 2 and 3, respectively, at the end of the study). In contrast, there was a progressive and significant decline of bone mineral density in untreated patients (-2.34 +/- 0.49%, P < 0.001). After 12 months serum calcium values in treated subjects were higher than in untreated patients (P < 0.05). Serum phosphate was raised only in Group 2, mean values being higher after 12 months than before treatment (P < 0.05); parathyroid hormone (PTH) declined in all treated patients, the fall being significant in Group 2 (P < 0.02). No important side effects were observed with treatment and no patient withdrew because of these. We conclude that cyclical low dose clodronate therapy induced a gain in lumbar spine bone mass in patients with postmenopausal osteoporosis.

The Effects of Vitamin D Receptor Polymorphism on Secondary Hyperparathyroidism and Bone Density After Renal Transplantation

Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for postrenal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels, and bone density in renal transplant recipients. We enrolled 69 patients (47 men and 22 women; mean age, 47 ± 11 years) who had undergone kidney transplantation 51 ± 5 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well as bone densitometry. VDR alleles were typed by a polymerase chain reaction (PCR) assay based on a polymorphic BsmI restriction site. When the patients were categorized according to the VDR genotype (BB, Bb, and bb), serum creatinine, and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (p < 0.05). PTH was significantly correlated to urinary type I collagen cross‐linked N‐telopeptide (NTx) values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (p < 0.02). In the whole population, only PTH (p < 0.05) and body mass index (BMI; p < 0.01) were independent predictors of spinal bone density. When grouping the patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R2 adj. = 0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.

BONE DISEASE IN PRIMARY HYPERCALCIURIA

Primary hypercalciuria (PH) is very often accompanied by some degree of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder, bone density is very frequently low, and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor nechrosis factor-α (TNF-α), are high in hypercalciuric patients. An excessive response to the acid load induced by dietary protein intake seems to be an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease, and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of parathyroid hormone (PTH) alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss in PH patients, possibly via the effect of mild-to-moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH patients. Even if most of the factors involved in this process have been identified, many aspects of this intriguing clinical condition remain to be elucidated.

Vertebral morphometry by X-ray absorptiometry before and after liver transplant: a cross-sectional study.

Objectives To evaluate bone density and fracture prevalence in patients with end-stage liver diseases (ESLD) awaiting liver transplant and in orthotopic liver-transplant (OLTx) recipients by using dual energy X-ray absorptiometry. Design In a cross-sectional study 27 patients (16 males and 11 females, mean age 49.9 ± 1.7 years) with ESLD, and 36 subjects (26 males and 10 females, mean age 50.5 ± 1.6 years) who had undergone OLTx 1–70 months before, were recruited. Methods All patients underwent biochemical assessment of mineral metabolism. Bone density measurement of the spine and femur and morphometric X-ray absorptiometry (MXA) of the vertebrae were also obtained. Results Bone density was decreased in both groups as compared to the expected normal values. Spinal density did not differ between the two groups, while femoral bone mass was lower in OLTx than in ESLD patients (T-scores of: femoral neck −1.91 ± 0.16 vs −1.12 ± 0.22, P < 0.01; total femur −1.62 ± 0.16 vs −0.94 ± 0.23, P < 0.02). Bone alkaline phosphatase was the only independent predictor of femoral density (R2 = −0.21, P < 0.05). Symptomatic fractures were reported by 25% of OLTx and 15% of ESLD patients. MXA vertebral fractures were present in 28% of OLTx and 7.5% of ESLD (P < 0.05) patients. Most of these fractures had been asymptomatic. Total methylprednisolone intake was higher in patients with MXA vertebral fractures than in non-fractured patients (P < 0.05). Conclusions Fragility fractures, especially of the spine, occur more frequently after liver transplantation, with corticosteroid treatment being the most important risk factor. Morphometric X-ray absorptiometry represents a useful technique for identifying vertebral fractures even in liver transplanted patients.

Lumbar osteoarthritis, bone mineral density, and quantitative ultrasound

Low bone mass is a major risk factor for osteoporotic fractures. Thus, bone density evaluation, performed by Dual Energy X-ray Absorptiometry (DXA) is important for diagnosis and monitoring treatment of osteoporosis. The accuracy of DXA, particularly at the lumbar spine, can be affected by several factors such as degenerative diseases. To evaluate the effects of vertebral osteophytosis on densitometric measurements, we examined 198 women, aged 32–81 years, who had undergone lateral X-ray of the lumbar spine. We classified patients according to different grades of osteophytosis, and evaluated bone density at the lumbar spine and the proximal femur by DXA. We also performed quantitative ultrasound at the heel (QUS). Patients with severe osteophytosis were significantly older (p<0.0005), and values were adjusted for this parameter. We observed a significant increase in lumbar bone density with worsening osteophytosis (p<0.02). On the contrary, no significant differences were found at the femur and QUS. According to bone density at the femoral neck, we subdivided patients into two groups: osteoporotic (group A) and non-osteoporotic (group B). Both groups showed increasingly high bone density at the spine with worsening osteophytosis (A: p<0.01; B: p<0.02). No differences were found in all the other evaluations. In conclusion, lumbar spine measurement is dramatically influenced by osteophytosis, particularly in the elderly. Consequently, other strategies should be performed such as evaluation of the hip and also measurement of the heel by ultrasound, which could be an interesting approach in these cases.

Declining trends in the incidence of hip fractures in people aged 65 years or over in years 2000–2011

BACKGROUND The aim of this study was to explore hip fracture (HFx) incidence in the Veneto Region of Italy, looking at potential differences with the national data. METHODS We analyzed HFx incidence for people aged 65years or over, in years 2000-2011, using data from the Regional Hospitalization Database. Patients were stratified by sex, calendar year and 5-year age class. Data for the single provinces of the Region were also obtained. Absolute number of HFx, crude incidence for 10,000 inhabitants and age-standardized fracture rates were calculated. RESULTS During the study period, there were 53,917 hospitalizations for HFx (77.7% in females). In the whole 11year period of observation, the absolute HFx number increased by 17.7% in males and 10.6% females, respectively. However, age-standardized incidence rates declined by 18% in the same period (IRR 0.82, 95% CI 0.78-0.87). This decreasing trend was almost identical through all the age-cohorts up to 84years. In the whole study period, HFx incidence was lower for Padova (IRR 0.63, 95% CI 0.60-0.66) and Verona (IRR 0.66, 95% CI 0.63-0.70) provinces as compared to the others. This regional profile was quite different with respect to the data published, for the same calendar years, for Italy as a whole, in spite of an almost identical demography of the population. CONCLUSIONS HFx incidence is declining in the Veneto Region of Italy. Further studies, aimed to investigate factors involved in this figure are needed.

Role of Diet in Calcium Nephrolithiasis

We evaluated the self-chosen customary diet of a group of 88 patients (50 males, age 42.9±11.8 (±SD) years; 38 females, age 44.0±14.7 years) affected by calcium nephrolithiasis (1) (Table 1). Sixty-four patients had recurrent, and 45 patients had bilateral nephrolithiasis. Mean body weights for the male (73.4±8.8 kg) and the female (65.0±12.2 kg) groups were 13% and 18%, respectively, above their ideal body weight.