calcitonin and pyridinoline

The aim of this study was to examine the effect of intranasal administration of salmon calcitonin to a group of 24 postmenopausal women with severe, established osteoporosis (t score < -2.5 SD) and more than one vertebral fracture. The patients were treated with 200 IU of nasal salmon calcitonin daily for 2 months with a subsequent pause of 2 months (3 cycles) and 500 mg calcium daily over a total of 12 months in an open randomized study. The patients were compared with an age matched control group of 18 women of a similar clinical status who were treated with calcium and vitamin D only. In the nasal calcitonin treatment group an increase in the trabecular axial bone density of 2.8% was achieved, as well as increase in trabecular appendicular (forearm) bone density of 1.6%, together with a cortical bone density increase of 1.8% axial and 1% appendicular. Initially, elevated values of urinary deoxypyridinoline were found in 12 women in the nasal calcitonin treatment group; these levels returned to normal under salmon calcitonin nasal therapy and documented the inhibition of increased osteoclastic activity. Cyclic intermittent calcitonin nasal therapy led to a general increase in trabecular and cortical axial and appendicular bone density, marked alleviation of the subjective sensation of pain, and a reduction in the daily dose of accompanying nonsteroidal anti-inflammatory drugs by 50%.

Topics: Administration, Intranasal; Amino Acids; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arm; Biomarkers; Bone Density; Bone Resorption; Calcitonin; Calcium; Female; Humans; Immunoenzyme Techniques; Middle Aged; Osteoporosis; Pain Measurement; Pilot Projects; Salmon; Spinal Fractures; Spine; Tomography, X-Ray Computed; Vitamin D

The usefulness of GH in the treatment of post-menopausal osteoporosis (PMO) is still debated. We have studied the effects of recombinant human GH (rhGH) given alone or in combination with salmon calcitonin (sCT) in the treatment of PMO.. Thirty women with established PMO (aged 61.1 +/- 4.4 years) were divided into 3 groups of 10 and randomly assigned to 3 treatment sequences: rhGH (12IU/day) s.c. for 7 days, followed by sCT (50 IU/day) s.c. for 21 days and by 61 days without treatment (group 1); placebo for 7 days, followed by sCT for 21 days and by 61 days without treatment (group 2); rhGH for 7 days, followed by placebo for 21 days, and by 61 days without treatment (group 3). Each cycle was repeated 8 times (24 months).. At days 0, 8, 29 and 90 of each cycle, serum IGF-I, calcium, phosphate, osteocalcin, alkaline phosphatase and urinary excretion of calcium, hydroxyproline and pyridinoline cross-links (Pyr) were measured. At months 0, 6, 12, 18 and 24, bone mineral density (BMD) was measured by dualphoton absorptiometry (DPA), at lumbar spine (LS), femoral shaft (F) and distal radius (DR).. A significant increase in serum osteocalcin and urinary calcium, hydroxyproline and Pyr was detected after each rhGH period. In group 1, BMD at lumbar spine increased by 2.5% at year 2; in contrast, significant (P < 0.05) decreases in BMD-LS values were found in patients treated with CT and placebo (group 2) and with GH and placebo (group 3). BMD-F did not show any significant change in patients of group 2, but a significant (P < 0.05) decrease was found in groups 1 and 3. BMD-DR did not show any significant change with respect to baseline in any of the three groups. No significant difference between the three groups was found in bone mass at the three different regions.. Our study demonstrates that treatment with rhGH increases bone turnover in postmenopausal osteoporotic women. Combined treatment with rhGH and CT over a period of 24 months is able to maintain bone mass at lumbar spine and distal radius, but induces a decline at femoral shaft; therefore, it does not seem particularly useful in the therapy of post-menopausal osteoporosis.

Topics: Amino Acids; Analgesics; Bone Density; Calcitonin; Calcium; Drug Therapy, Combination; Female; Femur; Human Growth Hormone; Humans; Hydroxyproline; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Placebos; Radius

In a double-blind, placebo-controlled, randomized group comparison, new and specific biochemical markers for bone resorption as follow-up parameters on the therapeutic response to nasal salmon calcitonin (sCT) were evaluated. Evaluation took place at an outpatient clinic where osteoporosis was being researched. The subjects included 208 women aged 68-72 treated for 2 years with either 50 IU, 100 IU, or 200 IU of nasal sCT or placebo; all groups received a daily calcium supplementation of 500 mg. Only 164 women fulfilled the study as valid completers. Markers were applied to frozen urine samples of a previously published intervention study of a new fasting urinary (fU) biochemical marker for bone resorption (CrossLapstrade mark, ELISA) and the urinary excretion of cross-links (pyridinoline and deoxypyridinoline) was measured, all corrected for creatinine. Bone mineral density of the lumbar spine and rates of vertebral and peripheral fractures were measured after 2 years of treatment. The creatinine corrected urinary pyridinoline, deoxypyridinoline, and CrossLaps showed maximum decreases of 10-43% (95% confidence interval -29.5% to 9.6% and -75.1% to 9.3%; P < 0. 01-0.001) after 6-9 months, after which the response leveled off. A significant difference among the four treatment groups was seen in fU CrossLaps (P < 0.01). The changes in spinal bone mass were significantly related to the decreases in fU CrossLaps: women with the highest response in spinal bone mass had decreases in fU CrossLaps of 44% (-83.5% to 7.4%) and women without response of 5% (-57.6% to 99.9%) P < 0.001). In women who fractured during the 2-year period, fU CrossLaps remained unchanged, whereas decreases of 30% (-75.1% to 44.7%) were seen in women who did not fracture (P = 0. 002). The results suggest that biochemical markers can be used to determine the optimum treatment regimen of nasal sCT. The response of the new marker, fU CrossLaps, significantly reflects the responses in bone mass of the spine and fracture rates.

Topics: Administration, Intranasal; Aged; Amino Acids; Biomarkers; Bone Density; Bone Resorption; Calcitonin; Double-Blind Method; Female; Follow-Up Studies; Humans

To evaluate the influence of synthetic salmon calcitonin (SMC) on bone resorption we investigated the modifications in urinary cross-links excretion [pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] induced by a single dose of the drug. The study was carried out in 16 healthy volunteers given a single dose of either 50 IU SMC I.M. or placebo, according to a double-blind, cross-over design. Urine was collected every 24 hours during the 72 hours after each treatment and Pyr and Dpyr were measured by an automated HPLC method. Pyr showed no significant difference after the two treatments, whereas in the first 24-hour urine collection Dpyr (nmol/24 hours +/- SD) was considerably lower after SMC than after placebo (118.9 +/- 26.0 against 147.2 +/- 45.0, P < 0.05). The amount of saved Dpyr was 19.2%. The selective effect of SMC on Dpyr excretion was more evident comparing the Pyr/Dpyr ratios for placebo and SMC during the first day of the study (4.1 +/- 0.6 against 4.8 +/- 0.7, respectively, P < 0.01). Using Eyre's formula (10 nmol Dpyr = 0.17 g bone) and assuming that no Dpyr is metabolized, the mean daily amount of bone resorbed was calculated (2.5 g for placebo and 2.0 g for SMC). The difference is the index of the bone-saving effect of SMC (0.48 g/day, or 19.2%). In conclusion, assuming that in healthy volunteers bone turnover is balanced with equal rates of formation and resorption, a dose of 50 IU I.M. of SMC reduces resorption, with a bone gain in the first 24 hours calculated as 9.4 mg/IU.

Topics: Adult; Amino Acids; Bone Resorption; Calcitonin; Chromatography, High Pressure Liquid; Cross-Over Studies; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Quality Control