Response Of Biochemical Markers Research Articles

Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates.

Alendronate has been approved as a first antiresorptive drug for treatment of osteoporosis in men. Except for fluoride, in some countries so far there has been no approved anabolic substance for the treatment of male osteoporosis. From small studies in men and male patients included in studies on postmenopausal osteoporosis there is sufficient evidence that fluoride has the same osteoblast-stimulating potency in men and women. In our own study on 64 men with idiopathic osteoporosis without prevalent fractures, a low-dose intermittent fluoride regimen (15 mg fluoride ions 3 months on, 1 month off) resulted in an average gain of lumbar spine BMD of 3% per year and a lower rate of incident fractures as compared with patients treated with calcium only. A combination of fluoride with an antiresorptive drug may improve the therapeutic results in terms of pattern of biochemical marker response and gain in BMD. This was shown for postemopausal osteoporosis in several studies using fluoride and hormone replacement therapy (HRT). Encouraged by a Dutch study using etidronate/fluoride in corticoid-induced osteoporosis, we performed a pilot study in 33 men with severe established primary osteoporosis giving cyclically etidronate for 14 days followed by fluoride plus calcium/vitamin D for 76 days. This combined regimen resulted in significantly higher increases of BMD than fluoride or etidronate alone. In an ongoing trial we are studying a continuous, combined treatment of alendronate and fluoride plus calcium/vitamin D in established idiopathic osteoporosis in men. The results of a preliminary evaluation look very promising. A large study with a bisphosphonate plus fluoride, taking fractures as the primary endpoint and bone biopsies to assess safety, would be very valuable.

Response of biochemical markers of bone turnover to estrogen treatment in post-menopausal women: evidence against an early anabolic effect on bone formation.

Bone loss following menopause can be prevented or reduced by estrogen replacement therapy (ERT). The primary action of estrogen on bone is generally considered to be antiresorptive, but some evidence would also suggest a stimulatory effect on bone formation. The aim of this study was to assess the effect of ERT on biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline), and of bone formation (bone-specific alkaline phosphatase--B-ALP, and the C-terminal propeptide of type I collagen--CICP) in a group of 25 postmenopausal women with no evidence of osteoporosis. Since the suggested anabolic effect of estrogen seems to take place in the early period of ERT, we measured the response of markers immediately before and after the start of treatment (30, 60, 120 and 180 days). The markers of bone resorption started to decrease at 30 days and remained low thereafter. We also observed a similar decrease in serum levels of B-ALP and CICP, reflecting a reduction of bone formation rate. Our data would indicate that ERT at the given dose does not have early anabolic effects on bone, in addition to its recognized suppressive effect on bone resorption.

Response of serum biochemical markers of bone metabolism totraining in the juvenile racehorse

Summary Sixteen Quarter Horse-type geldings were used to examine the response of biochemical markers of bone metabolism to forced exercise prior to and during race training. The study began when the average age of the horses was 15 months. Horses were exercised on a high-speed treadmill for 14 weeks, and were subsequently placed into race training. Serum was collected and assayed for concentrations of osteocalcin (BGP), the carboxyterminal telopeptide of type I collagen (ICTP) and the carboxyterminal propeptide of type I procollagen (PICP). When data were normalized from the onset of race training, ICTP and PICP concentrations were higher in the pre-exercised horses (P

INCIDENCE OF SKELETAL COMPLICATIONS IN PATIENTS WITH BONE METASTATIC PROSTATE CANCER AND HORMONE REFRACTORY DISEASE: PREDICTIVE ROLE OF BONE RESORPTION AND FORMATION MARKERS EVALUATED AT BASELINE

We evaluated the incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease. We also assessed the predictive role of bone turnover markers determined at baseline. A total of 112 patients were consecutively enrolled in our study from July 1990 to July 1998 and followed until death or the last followup. Bone pain, disease extent in bone, serum prostate specific antigen, hemoglobin, and a panel of bone formation and resorption markers were assessed at baseline before any second line treatment. Skeletal complications in 34 patients (30.3%, estimated yearly incidence 12.3%) involved vertebral deformity or collapse requiring spinal orthosis in 20 (17.9%), spinal cord compression in 7 (6.2%), pathological bone fracture in 10 (8.9%), symptomatic hypercalcemia in 1 (0.9%) and symptomatic hypocalcemia in 1 (0.9%). Median time to the evidence of the initial skeletal complication was 9.5 months. These adverse events did not influence overall survival. At baseline patients with eventual skeletal complications had greater bone pain (p = 0.02), a heavier tumor load in bone (p = 0.005), lower performance status (p = 0.05), and higher serum alkaline phosphatase (p <0.02) and urinary deoxypyridoline (p <0.05) than their counterparts. Multivariate analysis revealed that only urinary deoxypyridinoline was independently associated with the onset of these events (p <0.02). The scatterplot of urinary deoxypyridinoline values in patients with and without skeletal complications enabled us to detect a cutoff of 38 pM./mM. for predicting 51% of skeletal events with only an 8% false-positive rate. Skeletal complications are common in patients with prostate cancer and hormone refractory disease. Bone loss is the major cause of onset. Baseline deoxypyridinoline at the cutoff point noted had moderate sensitivity but high specificity for predicting these adverse skeletal events.

Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Response of biochemical markers of bone turnover to pamidronate infusion in Paget's disease of bone

Response of biochemical markers of bone turnover to pamidronate infusion in Paget's disease of bone