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Biomedical subjects

M J Välimäki

Publications and source records attributed to M J Välimäki.

At least 19 recordsLinked to original sources
PubMed2006

Vitamin D fortification of milk products does not resolve hypovitaminosis D in young Finnish men.

OBJECTIVE: To study if vitamin D fortification of milk products started in February 2003 has improved vitamin D status of young Finnish men, which has been poor before. DESIGN: A longitudinal study of one cohort. SETTING: Helsinki University Central Hospital. SUBJECTS: Sixty-five healthy men, studied for the first time in January 2001, were re-examined in January 2004. They were aged 18-21 years in 2001. METHODS: Blood was sampled for determination of serum 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH). 25-OHD was measured by both radioimmunoassay (RIA) and high-pressure liquid chromatography (HPLC). Consumption of milk, sour milk and fish and use of vitamin D supplements were assessed using a questionnaire. RESULTS: In January 2004, vitamin D fortification had raised serum 25-OHD level, with the mean of individual percent changes being 20.4% measured with RIA (P=0.0015). The correlation between the RIA and HPLC methods was high (r=0.85). Nineteen men (29.2%) had vitamin D deficiency (25-OHD<or=20 nmol/l) and 48 men (73.8%) had hypovitaminosis D (25-OHD<or=37.5 nmol/l). Serum 25-OHD and iPTH levels correlated inversely (r=-0.30; P=0.017). Serum 25-OHD levels were 52.0% higher for 13 vitamin D supplement users than for 51 non-users (P=0.0001). After exclusion of supplement users, an association between 25-OHD level and consumption of milk products was found (P=0.011), with the median vitamin D level being 6.5 nmol/l higher for those consuming four glasses of milk products or more daily than for those consuming one or less. Likewise, the higher the milk consumption, the higher the difference in 25-OHD between years 2004 and 2001 (P=0.0025). CONCLUSION: Vitamin D fortification of milk products slightly but insufficiently improved the poor vitamin D status of young Finnish men during winter. Further supplementation is warranted in order to normalize vitamin D levels and to support achievement of maximum peak bone mass. SPONSORSHIP: Supported by Paulo Foundation, Juho Vainio Foundation, Emil Aaltonen Foundation and Research Funding from Helsinki University Central Hospital (Erityisvaltionosuus).

Adolescent↗
PubMed2006

Quantitative ultrasound variables of the heel in Finnish men aged 18-20 yr: predictors, relationship to bone mineral content, and changes during military service.

INTRODUCTION: Determinants of BUA and SOS and their changes during military service-associated physical training were studied in 196 army recruits and 50 control men, aged 18-20 years. METHODS: Heel ultrasound measurement, DXA, muscle strength test, Cooper's running test and genetic analyses were performed. Lifestyle factors were recorded. Sex steroids and bone turnover markers were determined. Heel ultrasound was repeated after six months. RESULTS: Exercise was the most significant determinant of both BUA (p<0.0001) and SOS (p<0.0001). There were 10% and 1.3% differences in BUA (p=0.006) and SOS (p=0.0001), respectively, between men belonging to the lowest and highest quartiles of exercise index. Weight associated with BUA (p=0.005) and height with SOS (p=0.03). BUA and SOS correlated with BMC and BMD (p<0.0001) but explained only up to 21% of their variance. Over six months SOS increased more in recruits than in control men (p=0.0043), the increase being higher, the lower muscle strength at baseline (r =-0.27, p=0.0028). CONCLUSION: Exercise is the most important determinant of ultrasonographic variables in men, aged 18-20 years. Physical loading during military training increases SOS.

Adolescent↗
PubMed2006

Effects of alendronate and hormone replacement therapy, alone and in combination, on saliva, periodontal conditions and gingival crevicular fluid matrix metalloproteinase-8 levels in women with osteoporosis.

OBJECTIVE: To compare the effects of hormone replacement therapy (HRT), alendronate and their combination on oral health of elderly postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty patients, aged 65-80 years (mean 71 years), with a T-score of bone mineral density of -2.5 s.d. or less at either the lumbar spine or the femoral neck, were randomized to receive 2 mg of estradiol plus 1 mg norethisterone acetate (HRT) (n = 20), 10 mg of alendronate (n = 18), or their combination (n = 22) for 2 years. Periodontal and oral status and mouth symptoms were recorded, and salivary analyses made at the beginning and at the end of the study. Gingival crevicular fluid (GCF) matrix metalloproteinase (MMP-8) levels were determined to address destructive events in periodontal tissue. RESULTS: Resting salivary flow rate decreased by 19% (P < 0.05), and GCF MMP-8 tended to increase in the alendronate group. None of the regimens affected subjective feelings of dry or burning mouth. There were no significant changes in dental or periodontal status, stimulated flow rate or composition of saliva during the study. CONCLUSIONS: Alendronate decreased resting salivary flow rate but otherwise HRT or alendronate separately or in combination had no effect on oral health in elderly women with osteoporosis.

Aged↗
PubMed2005

Serum osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in bone loss?

PURPOSE: Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-kappaB ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss. METHODS: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex steroids--with or without pamidronate--prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy controls. RESULTS: Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls; in the two patient groups it increased by 26-27% at 6 months post-SCT (p=0.002-0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations were clearly elevated (p<0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients. CONCLUSION: Serum sRANKL concentrations may be modulated by bisphosphonates.

Absorptiometry, Photon↗
PubMed2005

Genetically defined adult-type hypolactasia and self-reported lactose intolerance as risk factors of osteoporosis in Finnish postmenopausal women.

OBJECTIVE: To study the relationships of molecularly defined lactose malabsorption (LM) and self-reported lactose intolerance (LI) to bone mineral density (BMD) and fractures among Finnish postmenopausal women. DESIGN: A cross-sectional study of two cohorts. SETTING: Helsinki University Central Hospital. SUBJECTS: One cohort was population-based and comprised 453 women, aged 62-78 (mean 69) y. Another comprised 52 women, aged 69-85 (mean 75) y, with osteoporotic fractures and 59 control women, aged 69-83 (mean 74) y, without osteoporosis. METHODS: A single nucleotide polymorphism of the lactase (LCT) gene at chromosome 2q21-22 was studied. It shows complete association with intestinal disaccharidase activity, with the genotype CC(-13 910) meaning adult-type hypolactasia (primary LM) and the genotypes CT(-13 910) and TT(-13 910) lactose absorption. BMD of the heel was measured by dual-energy X-ray absorptiometry (DXA). RESULTS: In the population-based cohort, 16.0% of women had self-reported LI but only 15.3% of them had the CC(-13 910) genotype. Calcium intake from dairy products (P = 0.10) and BMD, adjusted for age, weight, height, exercise, smoking, and estrogen use (P = 0.71) were similar for the genotypes. Women with self-reported LI had reduced calcium intake from dairy products (P < 0.0001) but they were more frequent users of calcium supplements than lactose-tolerants (P < 0.0001). Adjusted BMD was similar for lactose intolerant and tolerant women (P = 0.60). Of 104 women with previous fracture in the population-based cohort, 13.5% had the CC(-13 910) genotype, which did not differ from the prevalence of 19.3% among 347 women without fractures (P = 0.29). The frequency of the CC(-13 910) genotype (23.1%) for 52 women with established osteoporosis was similar as for 59 control women (15.3%) (P = 0.19). CONCLUSION: Molecularly defined LM and self-reported LI are not risk factors for osteoporosis, if calcium intake from diet and/or supplements remains sufficient. Our study confirms the poor correlation between self-reported LI and LM established by different techniques.

Aged↗
PubMed2004

Serum tartrate-resistant acid phosphatase 5b in monitoring bisphosphonate treatment with clodronate: a comparison with urinary N-terminal telopeptide of type I collagen and serum type I procollagen amino-terminal propeptide.

Osteoclastic tartrate-resistant acid phosphatase activity in serum (S-TRACP 5b) was measured in postmenopausal women ( n =59, mean age 56.1 years) with vertebral osteopenia before and during 2-year treatment with an 800-mg daily dose of clodronate, with a non-amino bisphosphonate. Changes in TRACP 5b were compared with those in urinary excretion of type I collagen amino-terminal telopeptide (U-NTX), corrected for creatinine excretion, a well-established marker of bone resorption, and to serum type I procollagen amino-terminal propeptide (S-PINP), a marker of bone formation. Marker changes 1 year after start of treatment were correlated with changes in bone mineral density (BMD). The least significant change (LSC) for each marker and BMD was calculated from values for subjects receiving placebo. Responders to treatment were those exhibiting a change larger than LSC. In response to clodronate treatment S-TRACP 5b (mean change up to -18%) decreased less than did U-NTX (up to -51%) or S-PINP (up to -46%). Marker changes correlated with changes in lumbar spine and trochanter BMD. The most efficient marker for finding responders to treatment was S-PINP, which changed more than the LSC (32%) in 72% of the subjects at the 1-year time point and in 79% at the 2-year time point. S-TRACP 5b change exceeded the LSC (27%) in 40% and 34% of the subjects at each time point, while U-NTX change exceeded the LSC (55%) in 55% and 40%, respectively. We conclude that, in terms of the proportion of subjects exhibiting any change exceeding the LSC, S-TRACP 5b did not appear to be superior to U-NTX and S-PINP in the follow-up of clodronate treatment. The reason may lie in the mechanism of action of clodronate, which rather than reducing the number of TRACP 5b-secreting osteoclasts, reduces the activity of bone proteolytic enzymes and thus the rate of bone organic matrix degradation. This is seen in decreased amounts of type I collagen breakdown products (U-NTX), and through coupling of bone resorption with bone formation, in a decrease in circulating levels of the marker that reflects new collagen formation (S-PINP).

Acid Phosphatase↗
PubMed2004

Molecularly defined lactose malabsorption, peak bone mass and bone turnover rate in young finnish men.

Lactose malabsorption (LM; adult-type hypolactasia), an autosomal recessive condition, results from the down-regulation of the activity of lactase enzyme in the intestinal wall. In previous studies the effect of LM on bone mass, bone turnover rate, development of osteoporosis and osteoporotic fractures has remained controversial. We have recently identified a single nucleotide polymorphism (SNP), a C to T change residing 13910 base pairs upstream of the lactase (LCT) gene at chromosome 2q21-22, which shows complete association with lactase persistence, with the C/C-13910 genotype defining LM and the genotypes C/T-13910 and T/T-13910 lactase persistence. The present study was undertaken to examine the relationship of the C/T-13910 polymorphism to peak bone mass, bone turnover rate, and stress fractures among young Finnish men. The study population comprised 234 young men, aged 18.3 to 20.6 years, 184 men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content (BMC), density (BMD), and scan area were measured in the lumbar spine and upper femur by dual-energy X-ray absorptiometry (DXA). Blood was sampled for genotyping of the C/T-13910 polymorphism and determination of serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), type I procollagen aminoterminal propeptide (PINP), and tartrate-resistant acid phosphatase 5b (TRACP5b). Second-void urine samples were collected for the determination of type I collagen aminoterminal telopeptide (NTX). The prevalence of the C/C-13910-genotype of these young adults did not differ significantly from the corresponding population prevalence of C/C-13910 (17.1% vs 18.1%) among Finnish blood donors. Fifteen recruits of the army experienced a stress fracture; 3 of them (20%) had the C/C-13910-genotype. Calcium intake was similar for the three genotypes as were the unadjusted BMCs, scan areas, and BMDs at different measurement sites. The adjustments for age, height, weight, smoking, alcohol consumption, and physical exercise in the multiple regression analysis did not reveal any significant relationships between the lactase genotypes and BMDs at lumbar (P = 0.16), femoral neck (P = 0.99) or total hip (P = 0.96) sites. Serum 25OHD, iPTH, and bone marker levels were similar for the C/C-13910 C/T-13910 and T/T-13910 genotypes. In summary, in young Finnish men, molecularly defined lactose malabsorption does not alter bone turnover rate and impair the acquisition of peak bone mass. Moreover, the C/C-13910 genotype does not seem to be a risk factor for stress fractures in army recruits.

Absorptiometry, Photon↗
PubMed2002

Prevention of bone loss by clodronate in early postmenopausal women with vertebral osteopenia: a dose-finding study.

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1-5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women ( T-score < or =-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% ( p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% ( p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% ( p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% ( p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400-800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials.

Absorptiometry, Photon↗
PubMed2002

Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation.

Osteoporotic fractures are potential long-term complications of bone marrow transplantation (BMT). We previously reported that bone mineral density (BMD) of patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6 months after BMT and that bone turnover rate was still increased 1 year after BMT. BMT patients do not need lifelong immunosuppressive treatment, which should offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13 men) of 29 long-term survivors of our previous study were invited to a follow-up study at a median of 75 months after BMT. From 12 months after BMT the BMD of the lumbar spine had increased by 2.4% (P = 0.002). The respective changes in femoral sites were +4.1% in the femoral neck (P = 0.087), 4.0% in the trochanter (P = 0.095), +4.7% in Ward's triangle (P = 0.072) and +1.4% in the total hip (P = 0.23). The markers of bone formation, serum osteocalcin and type I procollagen aminoterminal propeptide (PINP) had returned to control levels, but out of the markers of bone resorption the mean level of serum type I carboxyterminal telopeptide (ICTP) was 41% higher (P = 0.0001) and that of urinary type I collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P = 0.0002) in patients than in controls. The mean serum 25-hydroxyvitamin D [25(OH)D] was 33% lower in patients (P = 0.0002), most of whom had hypovitaminosis D [serum 25(OH)D < or = 37 nmol/l]. Except for two, males had serum testosterone level lower than before BMT and four men had hypogonadism. In conclusion, in long-term survivors of allogeneic BMT BMD recovers and bone turnover state normalizes as compared to the situation 1 year after BMT. More attention should be paid to the vitamin D status of all recipients and to possible hypogonadism of male patients.

Adult↗
PubMed2001

A high prevalence of hypovitaminosis D in Finnish medical in- and outpatients.

OBJECTIVE: To study the prevalence of hypovitaminosis D [serum 25(OH)D < or = 37 nmol L-1)] in Finnish medical in- and outpatients in a cross-sectional study. METHODS: The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured. RESULTS: Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L(-1) or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L(-1) or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males. CONCLUSION: Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population.

25-Hydroxyvitamin D 2↗
PubMed2000

Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (Calcitriol) for four years.

To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were enrolled in the study. Eighteen started a 4-year supplementation with 0.5 microg of calcitriol daily and 37 served as controls. Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol group, but decreased by 1.6% in the control group (P = 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P = 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0. 001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P = 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of calcium and suppressed serum PTH levels.

Absorptiometry, Photon↗
PubMed1999

A prospective study of bone loss and turnover after cardiac transplantation: effect of calcium supplementation with or without calcitonin.

Cardiac transplantation exposes recipients to osteoporosis and increased risk of consequent fractures. The purpose of the present study was to examine the magnitude, timing and mechanism of bone loss following cardiac transplantation, and to establish whether bone loss can be prevented by calcium with or without calcitonin. Thirty patients (29 men, 1 woman), aged 26-68 years (mean 48 years), were randomized into three groups of 10 to receive either no additional treatment, oral calcium 1 g twice daily for 12 months or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months. Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA) at the time of transplantation and 6 and 12 months later. Markers of bone formation [serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal propeptide (PICP) and aminoterminal propeptide (PINP)] and resorption [serum type I collagen carboxyterminal telopeptide (ICTP)], as well as serum testosterone in men, were assayed before transplantation and at 1 week and 1, 3, 6 and 12 months after transplantation. During the first 6 post-transplant months BMD calculated as a percent change from baseline decreased in the control group by 6.4% (p = 0.014) in the lumbar spine, by 6.0% (p = 0.003) in the femoral neck, by 5.0% (p = 0.003) in the trochanter and by 5.5% (p = 0.130) in Ward's triangle. Between 6 and 12 months a further decline in BMD occurred only at the three femoral sites, ranging from 2.2% to 9.8% (p = 0.004-0.079). In comparison with the control group, the group receiving calcium alone lost less bone in the trochanter between 0 and 6 months (p = 0.019), and the group receiving calcium together with calcitonin lost less bone in the femoral neck (p = 0.068) and Ward's triangle (p = 0.076) between 0 and 12 months. Seven (28%) of 25 assessable patients experienced vertebral compression fractures. Calcium with or without calcitonin had no effect on changes in biochemical parameters; consequently, the three study groups were combined. The markers of bone formation increased, the elevations in mean values being 59% for B-ALP at 1 month (p = 0.009), 152% for PICP at 1 week (p < 0. 0001) and 27% for PINP at 1 week (p = 0.021). After a temporary decline at 3 months B-ALP (p = 0.0002) and PINP (p < 0.0001) at 1 year were nearly doubled compared with baseline values. Throughout the study the marker of bone resorption, serum ICTP, was above normal, with a peak (mean values 67-69% above baseline) at 1 week (p = 0.0002) to 1 month (p < 0.0001). The mean concentration of total testosterone was decreased by 48% (p < 0.0001) 1 week and by 28% (p = 0.0005) 1 month after transplantation, but this was mainly explained by the concomitant drop in serum albumin. High bone turnover underlies bone loss after cardiac transplantation. Bone loss is most rapid during the first 6 post-transplant months. In the upper femur this bone loss may be reduced by treatment with calcium and calcitonin.

Adult↗
PubMed1999

A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin.

Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n = 22), or oral calcium 1 g twice daily for 12 months (n = 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P < 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.

Administration, Inhalation↗
PubMed1999

Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms.

PURPOSE: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL). PATIENTS AND METHODS: Eligible patients had the following substantial daily symptoms: for patients with carcinoid tumors, three or more stools and/or 1.5 or more flushing episodes; for patients with gastrinoma, greater than 50% elevated basic acid output; and for patients with vasoactive intestinal peptide-secreting tumors (VIPomas), four or more stools and/or a stool volume of >/= 800 mL, a measurable tumor, and an elevated biochemical tumor marker (>/= two times the upper limit of the normal reference range). Lanreotide PR was administered intramuscularly every 14 days at 30 mg for 6 months. We measured efficacy by studying symptoms, tumor markers, tumor size, and QOL. Side effects were scored according to the National Cancer Institute's toxicity grading system and ultrasound examination of the gallbladder. RESULTS: Fifty-five patients were included in the study (48 patients with carcinoid tumors, six patients with gastrinoma, and one patient with VIPoma). Symptomatic improvement (> 50% reduction) occurred in 38% of the assessable patients with carcinoid tumors, in 67% of the gastrinoma patients, and in the VIPoma patient. Tumor markers normalized in two of 45 assessable patients, 19 patients exhibited a reduction (> 50%), 19 patients exhibited no change, and tumor markers rose by more than 50% in five patients. Tumor size was reduced in two of 31 assessable patients and remained stable in 25 patients; four patients experienced progression. QOL assessments after 1 month showed improvements in emotional and cognitive function, and diminished fatigue, sleeping disorders, and diarrhea. Eight of 30 assessable patients developed gallstones. CONCLUSION: Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.

Adult↗