Higher Rates Of Bone Loss Research Articles

Laboratory markers predict bone loss in Crohn's disease: relationship to blood mononuclear cell function and nutritional status.

Crohn's disease is associated with reduced bone density. The power of simple markers of systemic inflammation to identify higher rates of bone loss, in Crohn's disease, is uncertain. This relationship and the role of circulating (peripheral blood) mononuclear cells were investigated in a case-control study. Urinary deoxypyridinoline/creatinine and serum osteocalcin concentrations were compared in male and premenopausal females with "active" Crohn's disease (C-reactive protein > or = 10 and/or erythrocyte sedimentation rate > or = 20) (n = 22) and controls with "quiescent" Crohn's disease (C-reactive protein < 10 and erythrocyte sedimentation rate < 20) (n = 21). No patients were receiving corticosteroid therapy. Production of tumour necrosis factor-alpha, interferon-gamma and prostaglandin E(2) by peripheral blood mononuclear cells were measured. Active Crohn's disease was associated with a higher deoxypyridinoline/creatinine (P = 0.02) and deoxypyridinoline/creatinine:osteocalcin ratio (P =0.01) compared with quiescent Crohn's disease, but similar osteocalcin (P = 0.24). These were not explained by vitamin D status, dietary intake or nutritional status. However, production of interferon-gamma by concanavalin A-stimulated peripheral blood mononuclear cells was lower in active Crohn's disease (P = 0.02) and correlated negatively with the deoxypyridinoline/creatinine:osteocalcin ratio (r = -0.40, P = 0.004). In Crohn's disease, raised C-reactive protein and erythrocyte sedimentation rate may indicate higher rates of bone loss and, if persistent, the need to assess bone mass even where disease symptoms are mild. This may be partly explained by altered production of interferon-gamma by peripheral blood mononuclear cells.

Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men.

Male osteoporosis is an increasingly important health problem. It is known that sex steroid hormones play an important role in regulating bone turnover and bone mass in males as well as in females. However, the exact mechanism of bone loss in men remains unknown. In the present study, 200 elderly men (age range, 55-85 yr) were followed for 4 yr to evaluate the relationships between hormone levels, bone turnover markers, bone mineral density, and rates of bone loss. Femoral and lumbar bone mineral density, bone ultrasound parameters at the os calcis, serum testosterone (T), serum estradiol (E(2)), SHBG levels, and bone turnover markers (urinary crosslaps and bone alkaline phosphatase) were evaluated for each man at enrollment and 4 yr afterward. The free androgen index (FAI) and free estrogen index (FEI) as well as measures of the bioavailable sex hormones [calculated bioavailable E(2) (c-bioE(2)) and T (c-bioT)] were calculated from total hormone levels and SHBG. In the total population, T, c-bioT, c-bioE(2), FAI, and FEI, but not E(2), decreased significantly with age, whereas SHBG increased significantly. Subjects with FEI, c-bioE(2), and E(2) levels below the median showed higher rates of bone loss at the lumbar spine and the femoral neck as well as higher speed-of-sounds decrease at the calcaneus with respect to men with FEI, c-bioE(2), and E(2) levels above the median. Serum bone alkaline phosphatase and urinary crosslaps were significantly higher in men with FEI, c-bioE(2), and E(2) in the lower quartile than in men with FEI, c-bioE(2), and E(2) levels in the higher quartile. No statistically significant differences were observed in relation to T, c-bioT, or FAI levels. Finally, the ratio between E(2) and T, an indirect measure for aromatase activity, increased significantly with age and was higher in normal than in osteoporotic subjects. In conclusion, results from the present study indicate an important role of estrogens, and particularly of the ability to aromatize T to E(2), in the regulation of bone loss and bone metabolism in elderly men.

Congestive heart failure is associated with the rate of bone loss.

To characterize relationships between mineral homeostasis, bone turnover, bone mass, and congestive heart failure (CHF), we evaluated 75 women with mild to moderate CHF. We examined the association in annual rate of change in spinal bone mineral density (BMD) with polymorphism of the vitamin D receptor (VDR) gene. Compared with the control group, the CHF group had reduced left ventricular ejection fraction (LVEF: 68.2 +/- 7.5% vs. 60.2 +/- 12.9%; P = 0.0249), human atrial natriuretic peptide (hANP) was elevated (hANP: 10.7 +/- 4.7 pmol L-1 vs. 25.8 +/- 24.2 pmol L-1; P = 0.001) and had lower peak VO2 (22.3 +/- 7.5 mL kg-1 min-1 vs. 15.8 +/- 7.4 mL kg-1 min-1; P = 0.0429). The CHF patients with the VDR FF genotype had a significantly high annual rate of decrease in BMD. In the CHF patients with the VDR FF genotype, urinary calcium excretion (FECa) was elevated (1.40 +/- 0.91% vs. 2.39 +/- 1.40%; P = 0.028), and serum bone-type alkaline phosphatase (B-ALP) was reduced (62.6 +/- 13.7 IU L-1 vs. 47.0 +/- 18.6 IU L-1; P = 0.0123). Also, FECa was correlated positively with furosemide dose (R = 0.881; P = 0.0087) and hANP concentrations (R = 0.635; P = 0.0147) and negatively with DeltaBMD (R = 0.72; P = 0.044) in the CHF patients with the VDR FF genotype. The CHF patients with the VDR FF genotype have higher rates of bone loss. These patients may need to increase their calcium intake and BMD may need to be followed more carefully over time.

Diagnosis and management of treatment-related osteoporosis in men with prostate carcinoma.

Osteoporosis is a complication of androgen deprivation therapy in men with prostate carcinoma. Androgen deprivation therapy, caused by either bilateral orchiectomy or treatment with a gonadotropin-releasing hormone agonist, decreases bone mineral density and increases fracture risk. Other factors including diet and lifestyle may contribute to bone loss. There is limited information regarding the best strategy to prevent osteoporosis in men with prostate carcinoma. Lifestyle modification including smoking cessation, moderation of alcohol consumption, and regular weight-bearing exercise should be encouraged. Supplemental calcium and vitamin D are also recommended. Additional treatment may be warranted for men with osteoporosis, fractures, or high rates of bone loss during androgen deprivation therapy. Intravenous pamidronate, a second-generation bisphosphonate, prevents bone loss during androgen deprivation therapy. Zoledronic acid, a more potent third-generation bisphosphonate, not only prevents bone loss but also increases bone mineral density during androgen deprivation therapy. Other bisphosphonates may be effective although they have not been evaluated in this clinical setting. Treatment with estrogens or selective estrogen receptor modulators may also be effective. Monotherapy with bicalutamide or other antiandrogens may cause less bone loss than androgen deprivation therapy.

Prevention of bone loss after cardiac transplantation with alendronate or calcitriol: efficacy and safety

The first year after cardiac transplantation (CTX) is characterized by high rates of bone loss and vertebral fracture. To prevent this complication of CTX, we conducted a 1-year, double-masked, randomized clinical trial (RCT) evaluating the efficacy and safety of alendronate (ALN; 10 mg QD) and calcitriol (1,25D; 0.25 mg BID). Subjects (n = 149) were randomized to ALN (n = 74) or 1,25D (n = 75), 21+/-11 days after CTX. Bone loss was compared between treatment groups and to a nonrandomized group of subjects (CON; n = 25) who declined to participate in the RCT. All participants received daily calcium (Ca; 1000 mg) and vitamin D (1000 IU) and immunosuppressive therapy. The 3 groups were similar with respect to gender, race, age, renal function, serum/urine Ca. Bone loss (% change from baseline at 1 year +/-S.E.M.) was analyzed by intent-to-treat (ITT) and on a subset that completed the RCT on study drug (Efficacy). Bone loss was minimal in treated groups and did not differ between ALN and 1,25D. Both sustained significantly less bone loss than CON. ∗SITEANALYSISALN1,25DCONLumbar SpineITT−0.8 ± 0.5−1.4 ± 0.6−3.2 ± 0.9Efficacy∗+0.3 ± 0.6−0.6 ± 0.8−3.2 ± 0.9Femoral NeckITT∗−1.5 ± 0.6−1.8 ± 0.8−6.2 ± 0.9Efficacy∗∗−1.3 ± 0.8−0.4 ± 0.8−6.2 ± 0.9∗p ≤ 0.001;∗∗p ≤ 0.0001 compared to CON. The 3 groups did not differ by immunosuppressive dose, hospitalizations, rejections or GI symptoms. Elevated urine Ca (≥ 300 mg/g) and serum Ca (≥ 10.4 mg/dl) were more frequent in 1,25D than ALN (p = 0.04 to 0.001).

Bisphosphonates to prevent osteoporosis in men receiving androgen deprivation therapy for prostate cancer.

Osteoporosis is an important complication of androgen deprivation therapy for prostate cancer. Androgen deprivation therapy either by bilateral orchiectomies or treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density (BMD) and increases the risk of fracture. Dietary factors and lifestyle may contribute to bone loss. There are limited prospective data about treatment or prevention of osteoporosis in men with prostate cancer and many recommendations are based on studies of postmenopausal osteoporosis. Lifestyle modification including smoking cessation, moderation of alcohol consumption, and regular weight bearing exercise should be encouraged. Supplemental calcium and vitamin D are recommended. Additional treatment may be warranted for men with osteoporosis, fractures, or high rates of bone loss during androgen deprivation therapy. Recent studies have evaluated the efficacy of bisphosphonates to prevent bone loss during androgen deprivation therapy. Pamidronate (pamidronic acid), a second-generation bisphosphonate, prevents bone loss in the hip and spine during androgen deprivation therapy. Zoledronic acid, a more potent third-generation bisphosphonate, not only prevents bone loss but also increases BMD in the hip and spine. Alendronate (alendronic acid) is approved for the treatment of osteoporosis in men although its efficacy and that of other oral bisphosphonates has not been evaluated in men receiving androgen deprivation therapy. Additional prospective studies are needed to evaluate the long-term effects of bisphosphonates on fracture risk and disease-related outcomes.

Osteoporosis during androgen deprivation therapy for prostate cancer

Osteoporosis is an important complication of androgen deprivation therapy (ADT). ADT by either orchiectomy or treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases fracture risk. Other factors, including diet and lifestyle, may contribute to bone loss in men with prostate cancer. Routine osteoporosis screening in men with prostate cancer is appropriate based on the high prevalence of osteoporosis. There is limited information about the best strategy to treat or prevent bone loss during ADT. Lifestyle modification, including smoking cessation, moderate alcohol consumption, and regular weight-bearing exercise should be encouraged. Supplemental calcium and vitamin D are also recommended. Additional treatment is warranted for men with osteoporosis, fractures, or high rates of bone loss during ADT. Pamidronate, an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective, although they have not been evaluated in this clinical setting. Alternative forms of hormonal therapy, including bicalutamide monotherapy, may cause less bone loss than ADT.

Association of physical activity and calcium intake with the maintenance of bone mass in premenopausal women.

Altogether 92 initially 25- to 30-year-old women of 132 original subjects participated in this 4-year follow-up study, which evaluated the influence of physical activity and calcium intake on the bone mineral content (BMC) of premenopausal women. The subjects were originally selected for a cross-sectional study according to their level of physical activity (high PA+ and low PA-) and calcium intake (high Ca+ and low Ca-), and the original groups were maintained in this follow-up study. The mean loss of BMC (95% CI) in the pooled data was 1.5% (0.7% to 2.4%) at the femoral neck, 0.6% (-0.8% to 1.9%) at the trochanter and 6.0% (4.5% to 7.4%) at the distal radius during the 4-year follow-up. According to repeated measures analyses of covariance neither physical activity nor physical fitness at baseline was associated with the rate of bone loss from the proximal femur. High calcium intake and the maintenance of body weight were both associated with a lower rate of bone loss from the proximal femur and distal radius. In addition, a long duration of breast feeding was associated with a higher rate of bone loss from the distal radius.

Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes

The role of caffeine as a risk factor for bone loss is controversial. Our goals were 1) to compare in both a cross-sectional study and a 3-y longitudinal study the bone mineral density (BMD) of postmenopausal women consuming high or low amounts of caffeine and 2) to study the interaction between caffeine intake, vitamin D receptor (VDR) polymorphism, and BMD in the longitudinal study. The results are derived from cross-sectional measurements of BMD in 489 elderly women (aged 65-77 y) and from longitudinal measurements made in 96 of these women who were treated with a placebo for 3 y. Changes in BMD were adjusted for confounding factors and were compared between groups with either low (< or =300 mg/d) or high (>300 mg/d) caffeine intakes and between the VDR genotype subgroups of the low- and high-caffeine groups. Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (-1.90 +/- 0.97% compared with 1.19 +/- 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (-8.14 +/- 2.62%) than did women with the TT genotype (-0.34 +/- 1.42%) when their caffeine intake was >300 mg/d. Intakes of caffeine in amounts >300 mg/d ( approximately 514 g, or 18 oz, brewed coffee) accelerate bone loss at the spine in elderly postmenopausal women. Furthermore, women with the tt genetic variant of VDR appear to be at a greater risk for this deleterious effect of caffeine on bone.

Osteopenia and osteoporosis in gastrointestinal diseases: diagnosis and treatment.

An increased awareness of the higher incidence of osteopenia and osteoporosis associated with a number of gastrointestinal disease states has occurred over the last few years. High rates of bone loss have been reported in luminal diseases such as inflammatory bowel disease and celiac disease as well as in cholestatic liver diseases and in the post-liver transplant setting. The post-gastrectomy state and chronic pancreatitis are also associated with decreased bone density. Publications over the last year have provided a better understanding of the true incidence of osteoporosis and fracture risk in these gastrointestinal disease states. Dual-energy x-ray absorptiometry remains the diagnostic procedure of choice. Biochemical markers of bone resorption have a role in identifying those patients with ongoing bone loss and monitoring their response to therapy. Identification of patients at risk and initiation of measures to prevent bone loss form the optimal therapeutic strategy. This article reviews advancements in the understanding of the development and activation of osteoblasts and osteoclasts. It also reviews the recent data concerning the diagnosis and treatment of bone loss associated with various gastrointestinal disease states.

Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men.

Estrogen appears to play an important role in determining bone mineral density in men, but it remains unclear whether estrogen primarily determines peak bone mass or also affects bone loss in elderly men. Thus, we assessed longitudinal rates of change in bone mineral density in young (22-39 yr; n = 88) vs. elderly (60-90 yr; n = 130) men and related these to circulating total and bioavailable estrogen and testosterone levels. In young men bone mineral density increased significantly over 4 yr at the mid-radius and ulna and at the total hip (by 0.32-0.43%/yr), whereas it decreased in the elderly men at the forearm sites (by 0.49-0.66%/yr), but did not change at the total hip. The rate of increase in bone mineral density at the forearm sites in the young men was significantly correlated to serum total and bioavailable estradiol and estrone levels (r = 0.22-0.35), but not with total or bioavailable testosterone levels. In the elderly men the rates of bone loss at the forearm sites were most closely associated with serum bioavailable estradiol levels (r = 0.29-0.33) rather than bioavailable testosterone levels. Moreover, elderly men with bioavailable estradiol levels below the median [40 pmol/liter (11 pg/ml)] had significantly higher rates of bone loss and levels of bone resorption markers than men with bioavailable estradiol levels above 40 pmol/liter. These data thus indicate that estrogen plays a key role both in the acquisition of peak bone mass in young men and in bone loss in elderly men. Moreover, our findings suggest that age-related decreases in bioavailable estradiol levels to below 40 pmol/liter may well be the major cause of bone loss in elderly men. This subset of men is perhaps most likely to benefit from preventive therapy.

A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women

Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. This was a prospective cohort study with a mean (+/-SD) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.

Quantitative computer tomography

Quantitative computed tomography (QCT) can determine the true volumetric bone density of trabecular and cortical bone separately and at any skeletal site. QCT, because of its sensitivity to changes in bone status, is widely accepted as the superior method for the axial skeleton because of the high responsiveness of spinal trabecular bone to osteoporotic changes. The precision and accuracy of QCT at this site are somewhat lower than the respective values of other densitometric techniques. Nevertheless, because QCT measures a higher rate of bone loss at early premenopausal age, it allows better estimation of risk of vertebral fracture and smaller time intervals between follow-up measurements. The clinical acceptance of QCT is constrained by limited access to CT scanners for bone densitometry, the higher degree of operator dependence and the inability of QCT to measure the femur. New developments currently in scientific trial show that using volumetric CT can increase precision of QCT at the spine and allow highly accurate, precise and meaningful measurements at the femur.

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women.

The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. Secondary analysis of a 10-year follow-up study (1979 1989) among postmenopausal women in the Netherlands. From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of < or = 0.5% over the first 5 years of the study and 35 women with a rate of > or = 2.5% per year. The isoflavonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry. Excretion of isoflavonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was significantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary fibre. Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens.

Bone Mass, Vitamin D Deficiency, and Hyperparathyroidism in Congestive Heart Failure

PURPOSE: In contrast to renal and hepatic failure, congestive heart failure (CHF) has not been associated with a defined metabolic bone disorder. However, low bone mass has been reported in patients with CHF who receive a cardiac transplant. Both the pathophysiology and therapy of CHF may influence bone and mineral homeostasis and evidence that calciotropic hormones may affect cardiovascular function is accumulating. Therefore, we evaluated patients with severe CHF to determine the prevalence of osteoporosis and to characterize relationships between mineral homeostasis, bone turnover, bone mass, and severity of CHF.PATIENTS AND METHODS: One hundred one patients (79 men and 22 women, aged 25 to 70 years) with severe CHF (New York Heart Association functional class III or IV) referred for consideration for cardiac transplantation were evaluated with measurements of serum 25-hydroxyvitamin D (25-OHD), 1,25 dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone (PTH), markers of bone turnover (serum osteocalcin, urinary hydroxyproline, and pyridinium crosslinks); bone mineral density (BMD) by dual energy x-ray absorptiometry was measured in 91 patients. Left ventricular ejection fraction (LVEF) and resting cardiac output (CO) were determined in 88 and maximal treadmill exercise testing and peak oxygen consumption were performed in 45 patients.RESULTS: Osteoporosis (T score ≤−2.5) was present in 7% at the lumbar spine, 6% at the total hip, and 19% at the femoral neck. Osteopenia (T scores between −1.0 and −2.5) was present in 43% at the lumbar spine, 47% at the total hip, and 42% at the femoral neck. Women were more severely affected (P = 0.007). Frankly low serum 25-OHD (≤9 pg/mL) and 1,25(OH)2D (≤15 pg/mL) levels were found in 17% and 26% of the patients, respectively, and elevated serum PTH (≥65 pg/mL) in 30%. Both low serum 1,25(OH)2D and increased serum PTH were associated with prerenal azotemia. Low serum vitamin D metabolites were associated with biochemical evidence of increased bone turnover, but BMD did not differ by vitamin D or PTH status. Patients with more severe CHF had significantly lower vitamin D metabolites and higher bone turnover, whereas elevated PTH was associated with better LVEF (21 ± 1 versus 18 ± 1%; P = 0.05) and correlated positively with resting CO (R = 0.220; P = 0.04).CONCLUSIONS: Osteopenia or osteoporosis were observed in approximately half of these patients with severe CHF. Abnormal calciotropic hormone concentrations, also common, were associated with evidence of increased bone resorption but were not related to BMD in this cross-sectional study. Abnormal concentrations of calciotropic hormones were related to the severity of cardiovascular compromise. Because both low BMD and low serum concentrations of 25-OHD in patients with CHF are associated with higher rates of bone loss and fracture after cardiac transplantation, patients should be evaluated for and receive appropriate therapy for these disorders.

Bone loss and turnover after cardiac transplantation.

Cardiac transplantation is associated with increased prevalence and incidence of fracture, and rapid bone loss has been reported during the first posttransplant year. To define further the pattern and etiology of bone loss after cardiac transplantation, we enrolled 70 patients (52 men and 18 women) in a prospective 3-yr study. Bone densitometry (BMD) and biochemical indexes of mineral metabolism were performed before and at defined times after transplantation. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), the mean rate of bone loss during the first year was 7.3 +/- 0.9% (+/- SEM) at the lumbar spine and 10.5 +/- 1.1% at the femoral neck. The rate of bone loss slowed (P < 0.001 compared to year 1) at both sites (0.9 +/- 0.9% and 0.1 +/- 1.0%, respectively) during the second year. During the third year, lumbar spine BMD increased at a rate of 2.4 +/- 0.8%/yr (P < 0.02 compared to year 2), but femoral neck BMD did not change. At the radius, the rate of decline in BMD was negligible during the first year (0.9 +/- 0.5%), but was significant during the second (2.1 +/- 0.6%; P < 0.01) and third (2.9 +/- 0.8%; P < 0.03) years. Evaluation of the pattern of bone loss during the first year demonstrated that mean lumbar spine BMD decreased rapidly during the first 6 months, after which there was no further decline. In contrast, femoral neck BMD continued to fall at an annualized rate of 8.2 +/- 1.3% during the second half of the year. The pattern and rates of bone loss were similar in men and women. Biochemistries revealed decreases in serum testosterone and osteocalcin and increases in all bone resorption markers 1 and 3 months after transplantation, with a return to baseline by 6 months. Higher rates of bone loss were associated with greater exposure to prednisone, lower serum concentrations of vitamin D metabolites, greater suppression of osteocalcin, higher levels of bone resorption markers, and, in men, lower serum testosterone concentrations. We conclude that rapid bone loss is primarily confined to the initial year after transplantation. During the first 6 months, bone loss is accompanied by alterations in markers of bone turnover consistent with biochemical uncoupling of bone formation and resorption. Greater exposure to glucocorticoids, lower serum concentrations of vitamin D metabolites and testosterone, and higher bone turnover were associated with more rapid bone loss.

Early increase in plama parathyroid hormone levels following liver transplantation

Background/Aims: The pathogenesis of post-transplantation bone loss is poorly understood, although glucocorticoid therapy is believed to play an important role. In the present study we have measured plasma parathyroid hormone concentrations in the first few months after orthotopic liver transplantation, in order to examine the potential contribution of hyperparathyroidism to bone disease. Patients and Methods: Twenty-seven patients aged 32–54 years, 12 male, undergoing liver transplantation were studied prospectively before and for 3 months after operation. Plasma parathyroid hormone and serum 25-hydroxyvitamin D concentrations were measured by radioimmunoassay. Results: Plasma parathyroid hormone levels were normal in all but two patients prior to transplantation. There was a highly significant increase in plasma parathyroid hormone concentrations at 1 and 2 months ( p<0.0005 and 0.001, respectively, versus baseline); by 3 months, values were close to those obtained preoperatively. Serum 25-hydroxyvitamin D concentrtions showed no significant change over the study period. However, 74% of the patients had subnormal values at baseline. Conclusions: An early and transient increase in plasma parathyroid hormone after liver transplantation may be responsible for the high rates of bone loss which occur during the first few post-operative months. Prevention of post-transplantation bone disease is most likely to be achieved by peri-operative intervention with an anti-resorptive agent.

New developments in biochemical markers for osteoporosis.

The noninvasive assessment of bone turnover has markedly improved in the past few years with the development of sensitive and specific markers of bone formation and bone resorption. Markers of bone formation in serum include total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen carboxyterminal extension peptide. Assessment of bone resorption can be achieved by measuring plasma tartrate-resistant acid phosphate and the urinary excretion (and possibly serum levels) of bone type I collagen degradation products: hydroxyproline, hydroxylysine glycosides, and, more recently, the pyridinium crosslinks (pyridinoline and deoxypyridinoline) and associated peptides. The immunoassay of human osteocalcin and bone alkaline phosphatase for formation and the pyridinoline crosslinks measured by high-pressure liquid chromatography or by immunoassay for bone resorption are currently the most sensitive and specific markers of bone turnover for the clinical assessment of osteoporosis. Using these new markers, several studies have shown that bone turnover increases after the menopause and remains elevated in late postmenopausal and elderly women. An increased bone turnover rate is related to a high rate of bone loss in postmenopausal women and to a decreased bone mass in elderly women. Recent data suggest that some of the new immunoassays for pyridinoline crosslinks could predict the subsequent risk of hip fracture in elderly women. Thus, bone markers might be used in combination with bone mass measurement to improve the prognostic assessment of postmenopausal women, i.e., their risk of developing osteoporosis and ultimately fractures. Treatment of postmenopausal women with antiresorptive drugs such as estrogens, bisphosphonates, and calcitonin induces a rapid decrease in the levels of bone markers that is correlated with the long-term effect of such treatments on bone mass. Thus, bone markers should be very useful in monitoring treatment efficacy in patients with osteoporosis.

The effects of high phosphorus intake on calcium homeostasis.

Survey data confirm that the dietary pattern of many American women who are at high risk of developing osteoporosis is typically high in phosphorus and low in calcium. The imbalance between calcium and phosphorus intake may become more pronounced with continued changes in food preferences and the growing use of phosphorus-containing food additives. Recent studies in young women have shown that a high phosphorus diet moderately low in calcium results in a mild secondary hyperparathyroidism that persists over 4 weeks. Plasma levels of calcitriol did not change despite changes in PTH and serum ionized calcium. Studies on men have shown that dietary phosphorus at levels within the normal range of intakes can affect the renal production and serum concentration of calcitriol. High phosphorus intakes for ten days reduced their plasma calcitriol levels; a 70% reduction in phosphate intake significantly increased their plasma calcitriol. Thus, several lines of evidence indicate that prolonged high phosphorus intake may impair the usual homeostatic mechanisms that come into play when dietary calcium is limited. This, in turn, could impair achievement of maximal bone mass or accelerate bone loss. Although no clinical studies have linked high phosphorus intake with lower bone mass or higher rates of bone loss in humans, this relationship has been demonstrated in animal models. For example, young beagles fed high phosphorus, moderately low calcium diets showed a significant reduction in vertebral bone mass. Current dietary patterns of high phosphorus, low calcium consumption result in persistent changes in calcium regulating hormones that are not conducive to maximizing peak bone mass during growth or slowing the rate of aging bone loss. The net effect of the present dietary pattern on bone status, particularly in teenage and young adult women, needs to be determined. Optimal nutrition early in life, which may include higher calcium and lower phosphorus intakes, together with adequate exercise, may be the most cost-effective approach to the prevention of osteoporotic fractures.

Hormone replacement therapy in chronic active hepatitis; a case report.

There is an increased incidence of osteoporosis in patients with chronic liver disease. Because patients with chronic active hepatitis (CAH) usually require corticosteroids for their liver disease prevention and treatment of bone loss presents a difficult problem. This case report describes a 41 year old female patient with CAH who had a high rate of bone loss. After an early menopause with noticeable menopausal symptoms, she was given transdermal oestrogen replacement therapy. The menopausal symptoms resolved completely, and there was no deterioration in her liver function tests or corticosteroid requirement. In addition, follow up quantitative bone mineral measurements over two years have shown improvement. This case shows the value of measurements of bone density, and oestrogen replacement therapy in CAH, even in the presence of continued corticosteroids.