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Measurement of bone turnover in prostate cancer patients receiving intermittent androgen suppression therapy.

Theyer G, Holub S, Olszewski U, Hamilton G - Open Access J Urol (2010)

Bottom Line: Serum CrossLaps concentrations peaked at the last 2 months of the AS phases (0.91 ± 0.25 μg/L; mean ± SEM) and were reduced below initial values (0.21 ± 0.43 versus baseline of 0.43 ± 0.06 μg/L) during therapy cessation periods until tumor progression-related increases.Measurements of the serum concentration of CrossLaps in prostate cancer patients receiving IAS indicated that treatment cessation phases rapidly reversed increased bone degradation associated with AS phases, in strong agreement with the clinical observations reporting reduced loss of BMD in IAS when compared to CAS.In terms of clinical outcomes, IAS seems to be as effective as CAS while showing reduced side effects, as demonstrated here by the reduction of androgen-induced bone matrix degradation.

View Article: PubMed Central - PubMed

Affiliation: Hospital Kittsee, Kittsee, Burgenland, Austria;

ABSTRACT

Purpose: Reports on clinical measurements of bone mineral density (BMD) in prostate cancer patients undergoing intermittent androgen suppression therapy (IAS) that allows for hormonal recovery between treatment cycles indicate decreased osteoporosis compared to continuous androgen suppression therapy (CAS). In the present study the effect of IAS on bone metabolism by determinations of CrossLaps, a biochemical marker of collagen degradation, were examined.

Method: In total 100 IAS treatment cycles of 75 patients with prostate cancer stages ≥ pT2 were studied. Clinical data and monthly laboratory tests (testosterone, prostate-specific antigen; PSA) of these patients were monitored together with measurements of C-terminal telopeptide collagen fragments using CrossLaps® ELISA assays.

Results: During phases of androgen suppression (AS) lasting for 9 months serum testosterone (<1 ng/mL) and PSA (<2 ng/mL) levels were reversibly reduced, indicating partial growth arrest and apoptotic regression of the prostatic tumors. Serum CrossLaps concentrations peaked at the last 2 months of the AS phases (0.91 ± 0.25 μg/L; mean ± SEM) and were reduced below initial values (0.21 ± 0.43 versus baseline of 0.43 ± 0.06 μg/L) during therapy cessation periods until tumor progression-related increases.

Conclusion: Measurements of the serum concentration of CrossLaps in prostate cancer patients receiving IAS indicated that treatment cessation phases rapidly reversed increased bone degradation associated with AS phases, in strong agreement with the clinical observations reporting reduced loss of BMD in IAS when compared to CAS. In terms of clinical outcomes, IAS seems to be as effective as CAS while showing reduced side effects, as demonstrated here by the reduction of androgen-induced bone matrix degradation.

No MeSH data available.


Related in: MedlinePlus

A–C) Mean time course of mean serum testosterone concentrations (A; values between months 1–9 of AS significantly below initial), mean serum PSA (B) and mean serum CrossLaps (C) for 100 IAS cycles observed in 75 patients (mean ± SEM; pretreatment value and months 1–9 of AS, followed by cessation period of IAS). Measurements of CrossLaps at eight and nine months of AS and between 19–51 months of treatment cessation are significantly different from the pretreatment value (P < 0.05).
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f2-oaju-2-155: A–C) Mean time course of mean serum testosterone concentrations (A; values between months 1–9 of AS significantly below initial), mean serum PSA (B) and mean serum CrossLaps (C) for 100 IAS cycles observed in 75 patients (mean ± SEM; pretreatment value and months 1–9 of AS, followed by cessation period of IAS). Measurements of CrossLaps at eight and nine months of AS and between 19–51 months of treatment cessation are significantly different from the pretreatment value (P < 0.05).

Mentions: Mean time courses of serum concentrations of testosterone (mean ± SEM) for 100 IAS cycles observed in 75 patients are shown in Figure 2A. Measurements of the initial and successive treatment cycles were overlaid. AS triggered decreases of testosterone to values <1 ng/mL, followed by recovery to baseline levels in the third month of treatment cessation. With some variation testosterone concentrations continued to remain near pretreatment values for up to 62 months in patients with a prolonged first treatment cessation period. Similarly, the time course of mean serum PSA concentrations (mean ± SEM) is presented in Figure 2B. During AS all patients showed reversible decline in PSA production to a mean level of <2 ng/mL. Treatment cessation resulted in recovery of PSA to approximately 5 ng/mL for up to 15 months, followed by further increases in the group of patients with prolonged responses and eventual tumor regrowth. The time course of CrossLaps concentrations as measured in 100 cycles of 75 patients representing a subpopulation of all IAS patients is shown in Figure 2C. Measurements at eight and nine months of AS and between 19 and 51 months of treatment cessation were significantly different from the pretreatment value (P < 0.05). Therefore, bone catabolism peaked at the end of the AS period (0.91 ± 0.25 μg/L) and fell below pretreatment levels (0.43 ± 0.06 μg/L) during treatment cessation (<approximately 0.2 μg/L) before regrowth of the tumor/metastasis induced further degradation of bone matrix.


Measurement of bone turnover in prostate cancer patients receiving intermittent androgen suppression therapy.

Theyer G, Holub S, Olszewski U, Hamilton G - Open Access J Urol (2010)

A–C) Mean time course of mean serum testosterone concentrations (A; values between months 1–9 of AS significantly below initial), mean serum PSA (B) and mean serum CrossLaps (C) for 100 IAS cycles observed in 75 patients (mean ± SEM; pretreatment value and months 1–9 of AS, followed by cessation period of IAS). Measurements of CrossLaps at eight and nine months of AS and between 19–51 months of treatment cessation are significantly different from the pretreatment value (P < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3818886&req=5

f2-oaju-2-155: A–C) Mean time course of mean serum testosterone concentrations (A; values between months 1–9 of AS significantly below initial), mean serum PSA (B) and mean serum CrossLaps (C) for 100 IAS cycles observed in 75 patients (mean ± SEM; pretreatment value and months 1–9 of AS, followed by cessation period of IAS). Measurements of CrossLaps at eight and nine months of AS and between 19–51 months of treatment cessation are significantly different from the pretreatment value (P < 0.05).
Mentions: Mean time courses of serum concentrations of testosterone (mean ± SEM) for 100 IAS cycles observed in 75 patients are shown in Figure 2A. Measurements of the initial and successive treatment cycles were overlaid. AS triggered decreases of testosterone to values <1 ng/mL, followed by recovery to baseline levels in the third month of treatment cessation. With some variation testosterone concentrations continued to remain near pretreatment values for up to 62 months in patients with a prolonged first treatment cessation period. Similarly, the time course of mean serum PSA concentrations (mean ± SEM) is presented in Figure 2B. During AS all patients showed reversible decline in PSA production to a mean level of <2 ng/mL. Treatment cessation resulted in recovery of PSA to approximately 5 ng/mL for up to 15 months, followed by further increases in the group of patients with prolonged responses and eventual tumor regrowth. The time course of CrossLaps concentrations as measured in 100 cycles of 75 patients representing a subpopulation of all IAS patients is shown in Figure 2C. Measurements at eight and nine months of AS and between 19 and 51 months of treatment cessation were significantly different from the pretreatment value (P < 0.05). Therefore, bone catabolism peaked at the end of the AS period (0.91 ± 0.25 μg/L) and fell below pretreatment levels (0.43 ± 0.06 μg/L) during treatment cessation (<approximately 0.2 μg/L) before regrowth of the tumor/metastasis induced further degradation of bone matrix.

Bottom Line: Serum CrossLaps concentrations peaked at the last 2 months of the AS phases (0.91 ± 0.25 μg/L; mean ± SEM) and were reduced below initial values (0.21 ± 0.43 versus baseline of 0.43 ± 0.06 μg/L) during therapy cessation periods until tumor progression-related increases.Measurements of the serum concentration of CrossLaps in prostate cancer patients receiving IAS indicated that treatment cessation phases rapidly reversed increased bone degradation associated with AS phases, in strong agreement with the clinical observations reporting reduced loss of BMD in IAS when compared to CAS.In terms of clinical outcomes, IAS seems to be as effective as CAS while showing reduced side effects, as demonstrated here by the reduction of androgen-induced bone matrix degradation.

View Article: PubMed Central - PubMed

Affiliation: Hospital Kittsee, Kittsee, Burgenland, Austria;

ABSTRACT

Purpose: Reports on clinical measurements of bone mineral density (BMD) in prostate cancer patients undergoing intermittent androgen suppression therapy (IAS) that allows for hormonal recovery between treatment cycles indicate decreased osteoporosis compared to continuous androgen suppression therapy (CAS). In the present study the effect of IAS on bone metabolism by determinations of CrossLaps, a biochemical marker of collagen degradation, were examined.

Method: In total 100 IAS treatment cycles of 75 patients with prostate cancer stages ≥ pT2 were studied. Clinical data and monthly laboratory tests (testosterone, prostate-specific antigen; PSA) of these patients were monitored together with measurements of C-terminal telopeptide collagen fragments using CrossLaps® ELISA assays.

Results: During phases of androgen suppression (AS) lasting for 9 months serum testosterone (<1 ng/mL) and PSA (<2 ng/mL) levels were reversibly reduced, indicating partial growth arrest and apoptotic regression of the prostatic tumors. Serum CrossLaps concentrations peaked at the last 2 months of the AS phases (0.91 ± 0.25 μg/L; mean ± SEM) and were reduced below initial values (0.21 ± 0.43 versus baseline of 0.43 ± 0.06 μg/L) during therapy cessation periods until tumor progression-related increases.

Conclusion: Measurements of the serum concentration of CrossLaps in prostate cancer patients receiving IAS indicated that treatment cessation phases rapidly reversed increased bone degradation associated with AS phases, in strong agreement with the clinical observations reporting reduced loss of BMD in IAS when compared to CAS. In terms of clinical outcomes, IAS seems to be as effective as CAS while showing reduced side effects, as demonstrated here by the reduction of androgen-induced bone matrix degradation.

No MeSH data available.


Related in: MedlinePlus