INSERM UMR 1033 et Université de Lyon, Lyon, France.
Bone. 2012 Oct;51(4):714-9. doi: 10.1016/j.bone.2012.07.004. Epub 2012 Jul 14.
Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (p<0.0001). This was associated with a trend of higher Tb.N, Tb.Th, DA, an inferior Conn.D and a lower bone turnover as shown by the decreases of osteoid parameters, MS/BS, Ac.f in LV1 when compared to IC. In addition, the ratio PYD/DPD was 4 times higher in LV1 than IC. After 3 months, significant decreases of sALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly only in LV1 (p<0.05) with a trend of increases in MS/BS and BFR/BS, compared to LV1-CTRL. In conclusion, in adult ewes, the bone mass, microarchitecture, remodeling and collagen crosslink content differ according to the bone site (iliac crest and vertebra). Furthermore, after 3 months, the responses to ZOL and TPTD were of different magnitude and delay between the two bone sites. The distinction of bone sites to study the early effects of anti-osteoporotic therapies appears meaningful in order to approach their site-specific anti-fracture efficacy.
髂嵴骨活检用于评估药物治疗的作用机制，但很少有数据比较该部位与易骨折部位。本研究的目的是比较两种不同骨部位对唑来膦酸和特立帕肽治疗的延迟和幅度的反应。评估唑来膦酸和特立帕肽对髂嵴和腰椎微结构、胶原交联和骨重塑的短期影响。老年母羊（n=8/组）接受 vehicle（CTRL）或单次唑来膦酸（ZOL，10mg）注射或每日特立帕肽（TPTD，20μg/d）治疗 3 个月。每月采集血样以评估骨转换标志物。在研究结束时，采集髂骨（IC）和 L1 腰椎（LV1）以评估骨微结构；吡啶啉（PYD）、脱氧吡啶啉（DPD）、戊糖（PEN）含量、骨重塑的静态和动态参数。在 CTRL 中，LV1 的 Tb-BV/TV 明显高于 IC（p<0.0001）。这与 LV1 的 Tb.N、Tb.Th、DA 呈趋势升高、Conn.D 较低以及骨转换率降低有关，表现为骨形成的骨表面参数、MS/BS、Ac.f 降低与 IC 相比。此外，LV1 中 PYD/DPD 比值是 IC 的 4 倍。3 个月后，ZOL 组的 sALP（p<0.001）和 sCTX（p<0.001）显著降低，而 TPTD 组在短暂升高后恢复到基线值。与各自的 CTRL 相比，ZOL 诱导 IC 中的 Tb.BV/TV、Conn.D、Tb.N 和 Tb.Sp 显著增加，但在 LV1 中则不然。无论部位如何，ZOL 均明显抑制骨转换：骨形成的静态参数显著降低，MS/BS、BFR/BS 和 Ac.f 的减少幅度为 -94%至 -98%（与 CTRL 相比，p<0.01 至 0.001）。这与 IC 皮质中 DPD 含量和 PYD/DPD 比值的降低有关。相比之下，3 个月后，TPTD 治疗除了在 IC 中观察到 Conn.D 升高的趋势外，并未改变 IC 和 LV1 的 3D 结构和微结构，与 IC-CTRL 相比。TPTD 治疗在 LV1 中引起皮质孔隙率显著增加（p<0.05），与 LV1-CTRL 相比。骨形成和吸收的静态参数在两个部位均增加，仅在 LV1 中显著增加（p<0.05），与 LV1-CTRL 相比，MS/BS 和 BFR/BS 呈上升趋势。总之，在成年母羊中，骨量、微结构、重塑和胶原交联含量根据骨部位（髂嵴和椎体）而不同。此外，3 个月后，ZOL 和 TPTD 的反应在两个部位的幅度和延迟存在差异。为了探讨其特定部位的抗骨折疗效，区分骨部位以研究抗骨质疏松治疗的早期效应似乎具有意义。
