Response to strict and liberalized specific carbohydrate diet in pediatric Crohn’s disease

AIM: To investigate the specific carbohydrate diet(SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease(CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple(diet alone, antibiotics or 5-ASA) or SCD with immunomodulators(corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.RESULTS: The mean age at start of the SCD was 11.8 ± 3.0 years(range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo(range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization(P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.     

Expressing effects of osteoporosis interventions in terms of postponing of fractures

OBJECTIVE: To estimate the effect from an osteoporosis intervention in terms of postponement of hip fractures. DESIGN: A Markov model using Nordic data on mortality and hip fracture incidence. PATIENTS: Women aged 50 years and older with increased risk of hip fracture. INTERVENTION: A hypothetical intervention that reduces the risk of hip fracture by 50%. MAIN OUTCOME MEASURES: Postponement of hip fractures--that is increase in expected fracture-free survival from osteoporosis interventions. RESULTS: A 1-year treatment would on average postpone hip fracture by 12 days if therapy were started at the age of 50 years and 23, 55, 90 or 74 days if the treatment were started at the ages of 60, 70, 80 or 90 years, respectively. For 10 years of treatment, the benefit was 146, 260, 369, 373 and 167 days, respectively. The younger the patient, the lower the risk of fracture and, consequently, the greater the benefit for those few who actually could benefit. CONCLUSIONS: The benefit in terms of average postponement of hip fractures from osteoporosis intervention was, other things being equal, greatest in women aged 70-90 years. Fracture postponement may represent an alternative to risk reductions in expressing the effect of osteoporosis interventions.     

Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study

OBJECTIVE: The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia. DESIGN: Case-control study. MEASUREMENTS: Fracture occurrence. PATIENTS: A self-administered questionnaire was issued to 537 consecutive patients with pituitary disorders excluding Cushing's disease. A total of 426 (79%) returned the questionnaire and 422 of these could be analysed. Each respondent was compared to three age- and gender-matched control respondents to the same questionnaire drawn randomly from the background population. RESULTS: The patients had a mean age of 51.4 +/- 14.8 years. One hundred and eight patients had acromegaly, 86 had prolactinomas, 136 had non-functioning pituitary adenomas (NFPA), 23 had craniopharyngiomas, and 73 had other types of pituitary disorders. For the total group the fracture risk was not elevated either before or after confirmed diagnosis compared to controls. However, among the patients with prolactinomas, the fracture risk was significantly increased before (relative risk, RR = 1.6, 95% CI: 1.1--2.3) but not after diagnosis. In patients with NFPA, fracture risk was borderline significantly elevated following diagnosis (RR = 1.6, 95% CI: 1.0--2.6). Patients with subnormal stimulated peak GH values suggestive of GH deficiency had a significantly higher risk of fractures after diagnosis than patients who had normal stimulated peak GH values (odds ratio, OR = 4.90, 95% CI: 1.10--21.88). CONCLUSIONS: Untreated prolactinomas were associated with a significant increase in fracture risk. Growth hormone deficiency was also associated with a higher fracture risk.     

Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis

The ideal treatment of osteoporosis should preferably prevent fractures through normalization of bone mass and bone micro-architecture. Biosynthetic human parathyroid hormone 1-34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2-3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 microg/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged.     

Spect bone scintigraphy in assessment of cranial Paget's disease

Single photon emission computed tomography (SPECT) bone scintigraphy was used in the assessment of Paget's disease in 3 patients with skull involvement. In comparison with conventional scintigraphy, SPECT improved the three-dimensional perception and made precise outlining of involved bones possible. The radionuclide uptake in lesions expressed as counts per pixel was 1.5 to 10 times that of normal bones. Routine use of SPECT in cranial Paget's disease for staging and monitoring the effect of treatment is proposed.     

Serum osteocalcin and bone isoenzyme alkaline phosphatase in growth hormone-deficient patients: Dose-response studies with biosynthetic human GH

Summary Serum osteocalcin and bone alkaline phosphatase (BAP) were measured in samples drawn at 8 a.m. in 7 patients with GH deficiency treated with recombinant human growth hormone (rhGH) (2 IU/day subcutaneously at 8 p.m.), and 7 normal controls. Patients treated with 2 IU/day had lower BAP than controls (P<0.05). Further, increasing doses of rhGH were given subcutaneously to each of the 7 patients for 3 consecutive 14-day periods (2, 4, and 6 IU/day at 8 p.m.) followed by 14 days off treatment. At the end of each period, the patient was hospitalized for frequent blood sampling from 8 p.m. to 11 a.m. the following day. A dose-dependent increase in area under the curve (AUC) was seen for osteocalcin (P<0.05), whereas the increase in AUC for BAP just failed to reach significance (P<0.10). The nocturnal patterns of serum osteocalcin in patients on 4 and 6 IU/day were statistically indistinguishable from those in controls. During treatment with 2 IU/day and the off-treatment period, the pattern was significantly different from controls (P<0.05). In conclusion, rhGH has a dose-dependent effect on basal osteoblastic activity and the nocturnal pattern of osteocalcin. Serum osteocalcin increases within hours following rhGH administration. However, 2 IU/day is inadequate to maintain normal levels and nocturnal variation in markers of osteoblastic activity.     

Diurnal rhythm in serum osteocalcin: Relation with sleep,growth hormone,and PTH(1–84)

Summary We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1–84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with norsleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P>0.50). Serum OC (mean±SE) was 30.9±2.5 μg/liter during sleep (2330-0730 hours) versus 29.9±4.9 μg/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P<0.01). A maximum GH peak (mean±SE) of 10.3±2.4 μg/liter occurred at 0136 hours±6 minutes during sleep compared with a maximal peak of 7.6±1.2 μg/liter (P<0.01) at 0245 hours ±20 minutes (P<0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61±0.60 μg/liter compared with 2.39±0.40 μg/liter during sleep deprivation (P<0.005). Small insignificant changes occurred in serum PTH(1–84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1–84) remains unsettled.     

Diurnal rhythm in serum activity of wheat-germ lectin-precipitable alkaline phosphatase: temporal relationships with the diurnal rhythm of serum osteocalcin

Serum levels of osteocalcin (S-OC) and lectin-precipitable alkaline phosphatase activity (S-LAP) are sensitive markers of osteoblastic activity. Diurnal variation has been found for S-OC but has not been reported for S-LAP. We measured S-LAP and serum total alkaline phosphatase (S-TAP) in samples drawn every 60 min during a 24-h study period in nine normal subjects and correlated the findings with the diurnal variation in S-OC. A significant (p less than 0.05) diurnal variation in S-LAP characterized by peaks at 1430 hours and 2330 hours and nadir at 0630 hours was found. Peak levels were 30% higher than nadir level (p less than 0.05). S-TAP also varied significantly (p less than 0.05) with nadir at 0630 hours, showing a difference of 23% between peak and nadir levels (p less than 0.05). Significant cross-correlation was found between S-OC and S-LAP and S-TAP when these lagged 4 h after S-OC: r = 0.51 (p less than 0.02) and r = 0.65 (p less than 0.003), respectively. In other words, changes in S-LAP and S-TAP preceded changes in S-OC by 4 h. There were no significant cross-correlations between the non-lectin-precipitable fraction of AP and S-OC. In conclusion, S-LAP varies in a diurnal rhythm closely related with the diurnal rhythm of S-OC. The almost similar patterns in the diurnal serum levels of these two osteoblastic products strongly suggest that osteoblastic activity fluctuates rhythmically during the day in humans.     

Patients with eating disorders. A high-risk group for fractures

PURPOSE: To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders). DESIGN: Clinical overview. FINDINGS: Bone mineral density is decreased and fracture risk increased in patients with anorexia nervosa. In patients with bulimia nervosa, bone mineral is only marginally decreased and fracture risk marginally increased. In patients with other eating disorders (eating disorders not otherwise specified), bone mineral density is decreased and fracture risk increased. CONCLUSIONS: Fracture risk is increased in patients with eating disorders. An eating disorder should be suspected in severely underweight young individuals (primarily girls) presenting with fractures, especially low-energy fractures.