Calcium supplements lower bone resorption after renal transplant.

AIM: Bone loss in renal transplant (RT) patients is a problem that begins during end-stage kidney disease and persists after transplantation. Suppression of parathyroid hormone (PTH) may decrease bone loss and improve fracture rate. METHODS: A single-group prospective intervention study involving 30 patients was performed at a large RT unit. Investigations included dual-emission X-ray absorptiometry scan, vertebral X-ray, calcium absorption test, 24-h urinary calcium and serum measurements of total and ionized calcium, PTH, C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, 25 hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D3. Patients were given 500 mg elemental calcium daily for seven d, and serum measurements were repeated. RESULTS: Two-tailed Wilcoxon rank-sum test showed significant decreases in PTH (p<0.01) and CTX (p<0.01) after calcium load. Dietary calcium, mean calcium absorption, and urinary calcium excretion were below desirable levels. Mean 25 hydroxyvitamin D (25(OH)D) was low, but levels of 1,25-dihydroxyvitamin D3 were normal. Calcium absorption significantly correlated with change in PTH (p<0.001), baseline 25(OH)D (p<0.001), and mycophenolate dose (p=0.024). CONCLUSIONS: Calcium malabsorption is prevalent in RT recipients, contributing to bone destruction and compounded by poor dietary intake and low 25(OH)D. Calcium supplementation appears to help overcome this deficiency and acutely suppress PTH. Calcium may be an effective and inexpensive therapy for bone loss in RT recipients.

Calcium malabsorption does not cause secondary hyperparathyroidism.

We challenge the widespread assumption that malabsorption of calcium per se causes secondary hyperparathyroidism. Serum parathyroid hormone (PTH) does not rise at the menopause despite the fall in calcium absorption, nor is it raised in osteoporotic women with vertebral fractures despite their low calcium absorption. The age-related rise in serum PTH can be accounted for by the age-related fall in serum 25(OH)D and/or decline in renal function with consequent loss of the calcemic action of vitamin D on bone. The reference interval for serum PTH is established in the fasting state when it is at the top of its diurnal cycle and is maintaining serum ionized calcium at the expense of bone to meet the calcium being lost through skin, bowel, and kidneys. There is no evidence that the fasting PTH is influenced by the previous day's intake or absorption of calcium, although it can be lowered by a large evening calcium supplement. Malabsorption of calcium-like dietary calcium deficiency-is a risk factor for osteoporosis because it reduces or prevents the normal food-related daytime fall in PTH and bone resorption, not because it causes secondary hyperparathyroidism.

Pituitary involvement in Wegener's granulomatosis.

Wegener's granulomatosis (WG) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis of small and medium-sized vessels. Pituitary involvement in WG is rare with only 22 previous case reports in the English medical literature between 1966 and 2006. Herein we report another patient with WG-related diabetes insipidus (DI) and partial disruption of the anterior pituitary axes. We also review the clinical features, imaging findings, treatment and outcome of WG-related pituitary involvement. Isolated pituitary involvement in the absence of lung or renal complications in WG is rare and described in only one previous patient. Pituitary involvement in WG is usually associated with other organ involvement (96% of cases)-commonly upper respiratory tract (93%), lungs (73%) and kidneys (67%). Abnormalities are often seen in the hypothalamo-pituitary region on magnetic resonance imaging (MRI) or computed tomography (CT) of the head (90% of cases). In 65% of reported cases, cyclophosphamide-based induction therapy was used with a subsequent relapse rate of 27%, occurring at a median of 10.5 months (range: 7-36 months) after initiation of treatment. In comparison, induction treatment without cyclophosphamide was associated with relapse in 50% at a median of 4.5 months (range: 4-18 months after starting treatment) suggesting more frequent and earlier relapse. Therefore, we recommend treatment with cyclophosphamide-based regimen. Despite treatment of WG, only 17% (4 patients) had full recovery in their pituitary function. The long-term prognosis of patients with WG and pituitary involvement is not known.

Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass.

Little is known about the effects on the skeleton of laparoscopic Roux-en-Y gastric bypass (LRGB) surgery for morbid obesity and subsequent weight loss. We compared 25 patients who had undergone LRGB 11 +/- 3 months previously with 30 obese controls matched for age, gender, and menopausal status. Compared with obese controls, patients post LRGB had significantly lower weight (92 +/- 16 vs. 133 +/- 20 kg; P < 0.001) and body mass index (31 +/- 5 vs. 48 +/- 7 kg/m(2); P < 0.001). Markers of bone turnover were significantly elevated in patients post LRGB compared with controls (urinary N-telopeptide cross-linked collagen type 1, 93 +/- 38 vs. 24 +/- 11 nmol bone collagen equivalents per mmol creatinine; and osteocalcin, 11.6 +/- 3.4 vs. 7.6 +/- 3.6 ng/ml; both P < 0.001). Fifteen patients were studied prospectively for an average of 9 months after LRGB. They lost 37 +/- 9 kg and had a 29 +/- 8% fall in body mass index (both P < 0.001). Urinary N-telopeptide cross-linked collagen type 1 increased by 174 +/- 168% at 3 months (P < 0.01) and 319 +/- 187% at 9 months (P < 0.01). Bone mineral density decreased significantly at the total hip (7.8 +/- 4.8%; P < 0.001), trochanter (9.3 +/- 5.7%; P < 0.001), and total body (1.6 +/- 2.0%; P < 0.05), with significant decreases in bone mineral content at these sites. In summary, within 3 to 9 months after LRGB, morbidly obese patients have an increase in bone resorption associated with a decrease in bone mass. Additional studies are needed to examine these findings over the longer term.

Does bone mineral density and knowledge influence health-related behaviors of elderly men at risk for osteoporosis?

To determine if bone mineral density (BMD) substantially influences health-related behaviors in men at risk for osteoporosis, we surveyed 102 men who were participating in a study of prostate cancer and bone loss. Subjects included 68 men with prostate cancer, 44 of whom were hypogonadal on androgen deprivation therapy, and 34 healthy age-matched controls without prostate cancer. At least 6 mo after an initial evaluation, assessment of BMD, and osteoporosis information session, men were administered a questionnaire regarding their healthrelated behaviors. We found that men with osteopenia were 4 times as likely (13%) and men with osteoporosis were more than 10 times as likely (41%) to start taking bisphosphonates compared to men with a normal bone mass (3%, p < 0.0001). Men with low bone mass were more likely to begin taking calcium (p < 0.05) and vitamin D supplements (p < 0.05). Hypogonadal men were 10 times as likely to begin using bisphosphonates (34%) compared to the control group (3%, p < 0.0001) and twice as likely to begin using calcium supplements (57% vs 24%, p < 0.05). Caffeine consumption, alcohol consumption, dietary calcium intake, exercise, and smoking habits were not different in men with osteoporosis or those who were hypogonadal compared to controls. We conclude that men with low bone mass and hypogonadism were more likely to start using bisphosphonates, calcium supplements, and vitamin D supplements after having a bone density test. However, they were not more likely to make significant health-related lifestyle changes after obtaining the results of their bone mass.

The correlation between third-trimester maternal and newborn-serum 25-hydroxy-vitamin D in a selected South Australian group of newborn samples.

BACKGROUND: Although vitamin D insufficiency is prevalent in the community, only a few population-based studies have measured serum 25-hydroxy-vitamin D (25OHD) levels during pregnancy and in newborns. Maternal vitamin D deficiency has been linked to pregnancy complications, as well as hypocalcaemia and rickets in the newborn. Here, the authors report third-trimester maternal and newborn-serum 25OHD concentrations in 101 neonates whose serum samples were sent for testing. METHODS: The newborn 25OHD levels were correlated with the third-trimester maternal serum 25OHD levels using a least-square regression analysis. All samples were measured using an enzyme immunoassay (EIA). Ten randomly selected newborn serum samples were also measured using liquid chromatography/tandem mass spectrometry LC-MSMS, and correlated with the EIA method. RESULTS: Out of 99 mothers of the newborns, only 19, 42 and 68 had their 25OHD level measured in the first, second and third trimester respectively. The mean maternal age was 30 years, while the mean maternal third-trimester 25OHD concentration was 48 nmol/l. Of the newborns, 53% were female, and 85% were term deliveries. The mean newborn-serum 25OHD was 68 nmol/l. Neonatal 25OHD was related to maternal third-trimester levels measured by EIA (r=0.3; newborn 25OHD=0.42(maternal 25OHD)+44.2; p=0.02). EIA and LC-MSMS concentrations for newborns correlated significantly over a range between 20 and 103 nmol/l by EIA (r=0.9; EIA=1.04(LCMSMS)+10.1; p<0.00 (slope); p=0.18 (intercept)). The mean 25OHD concentration in women who suffered pre-eclampsia and premature rupture of membranes were 45 and 39 nmol/l respectively. CONCLUSIONS: Newborn-serum 25OHD concentrations depend on the maternal circulating plasma 25OHD level at least during the third trimester. Neonatal 25OHD levels obtained by EIA correlated well with LC-MSMS. Although the EIA values for neonates were greater than LC-MSMS values, this difference was not statistically significant.

Hyperparathyroidism and vitamin D deficiency predispose to bone loss in renal transplant recipients.

BACKGROUND: Bone disease is common postrenal transplantation resulting in increased fracture rates and morbidity. The cause is multifactorial including hyperparathyroidism, corticosteroids, and possibly calcium and vitamin D deficiencies. The aim of this study was to identify modifiable factors contributing to bone disease in long-term renal transplant (RT) recipients. METHODS: Ninety-seven RT recipients were prospectively recruited over a 6-month period from a single center. Bone-related parameters were collected including bone mineral density at lumbar spine and total hip sites, serum and urinary markers of bone-turnover and calcium metabolism, and intact parathyroid hormone levels. RESULTS: The mean time posttransplant of RT recipients was 9.5 years and mean estimated glomerular filtration rate was 70.3 mL/min. Up to 50% of recipients had biochemical evidence of calcium and vitamin D deficiencies. In the multiple regression models, elevated intact parathyroid hormone levels and calcium deficiency, which are affected by estimated glomerular filtration rate and vitamin D levels, are significantly associated with reduction in bone mineral density measurements. CONCLUSIONS: Hyperparathyroidism and vitamin D deficiency are common and are likely to contribute to bone loss postrenal transplantation. Measures aim to correct these problems pre- and posttransplant may improve bone health in RT recipients.

Vitamin D metabolites and calcium absorption in severe vitamin D deficiency.

Contrary to frequent claims, vitamin D insufficiency does not generally cause malabsorption of calcium because serum 1,25(OH)(2)D, which is the major determinant of calcium absorption, is maintained by secondary hyperparathyroidism. Nevertheless, because malabsorption of calcium has been described in osteomalacia, there must be a 25(OH)D level below which the serum 1,25(OH)(2)D can no longer be sustained, although it has never been defined. This paper seeks to define it. We examined the records of 3661 patients and found 319 with a serum 25(OH)D < or = 40 nM, in whom calcium absorption, serum calcium, PTH, bone markers, and vitamin D metabolites had been measured. They were grouped according to their serum 25(OH)D into four categories, 0-10, 11-20, 21-30, and 31-40 nM, and differences between the groups were tested by ANOVA. Correlations between the variables were also examined. Serum calcium, 1,25(OH)(2)D, and calcium absorption were significantly decreased and serum PTH and alkaline phosphatase (ALP) and urine hydroxyproline were increased in those with 25(OH)D < or = 10 nM. Serum ALP and urine hydroxyproline were more strongly related, inversely, to calcium absorption than to the vitamin D metabolites. We conclude that vitamin D deficiency does not reduce serum 1,25(OH)(2)D, and therefore calcium absorption, until the serum 25(OH)D falls to approximately 10 nM. At this level, the substrate concentration seems to be insufficient to maintain the level of the dihydroxy metabolite despite secondary hyperparathyroidism. Further studies are needed to see how these changes correlate with the histological changes of osteomalacia.

The management of osteoporosis following hip fracture: have we improved our care?

To determine if physicians have improved the recognition and treatment of osteoporosis in patients with an acute hip fracture, we performed a retrospective analysis of discharge data from 1995 and 2000 at the University of Pittsburgh Medical Center, a large tertiary care, academic institution. We examined patients admitted with an acute hip fracture in 1995 and 2000 and age- and sex-matched patients admitted with community acquired pneumonia in 2000. Outcomes included age, gender, race, discharge diagnoses (from ICD-9 codes) and discharge medications (from discharge summaries) in all patients. There were 136 acute hip fracture patients (mean age 73+/-18 years) in 1995, 117 acute hip fracture patients (mean age 76+/-16 years) in 2000 and 116 patients with community-acquired pneumonia (mean age 78+/-7 years). Patients admitted in 2000 with an acute hip fracture were more likely to be diagnosed with osteoporosis (18% vs. 4%, P<0.02), more likely to be discharged on calcium (17% vs. 7%, P<0.02) and more likely to be discharged on antiresorptive therapy (15% vs. 2%, P<0.001) than those admitted in 1995. Moreover, patients admitted with community-acquired pneumonia were just as likely to receive calcium, vitamin D or antiresorptive agents at the time of discharge as those with an acute hip fracture in 2000. Patients with a diagnosis of osteoporosis in 2000 were older and more likely to receive antiresorptive agents than those without a diagnosis (29% vs. 11%, P<0.05). None of the patients received a bone mineral density examination while in the hospital. Although there was an improvement in the management of osteoporosis after an acute hip fracture from 1995 to 2000, there was no difference in management of patients with hip fracture versus pneumonia in the year 2000. However, patients with a "diagnosis" of osteoporosis in 2000 were more likely to be discharged on appropriate therapeutic options. We conclude that although we have improved our care of osteoporosis for elderly in general from 1995 to 2000, patients with an acute hip fracture are not receiving any additional treatment unless they have a diagnosis of osteoporosis. Further studies are needed to determine which factors are needed to target patients for appropriate diagnosis and treatment.