Miyamura Gaku, Wakabayashi Hiroki, Nagao Nobuto, Kato Sho, Nakagawa Taro, Naito Yohei, Sudo Akihiro
Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
Mod Rheumatol. 2021 May;31(3):733-742. doi: 10.1080/14397595.2020.1782592. Epub 2020 Jul 10.
There are few reports on the comparison between teriparatide (PTH) and bisphosphonate (BP) in terms of osteoporosis pain-related behavior and immunohistochemical findings. The aims of this study were to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of PTH and BP on pain and bone loss in hind limb-unloaded (HU) mice. The mechanism of osteoporotic pain in HU mice was evaluated by examining pain-related behavior and immunohistochemical findings. The effects of PTH and alendronate (ALN), a potent osteoclast inhibitor, on these parameters were also assessed.
Eight-week-old male ddY mice were tail-suspended for 2 weeks and assigned to four groups: hind limb-loaded (HL) mice with only tail suspension treated with vehicle; HU mice with tail suspension treated with vehicle; HU mice treated with PTH; and HU mice treated with ALN. Starting immediately after reloading, vehicle, PTH, or ALN was injected subcutaneously. After a 2-week treatment, mechanical sensitivity was examined using von Frey filaments. Bilateral hind limbs were removed for micro-computed tomography, immunohistochemical analysis, and messenger RNA (mRNA) expression analysis.
HU mice with tail suspension developed bone loss and mechanical hyperalgesia in the hind limbs. The HU mice showed an increased osteoclasts and sclerostin-positive cells in the hind limb bone. Furthermore, PTH and ALN both prevented HU-induced bone loss and mechanical hyperalgesia in the osteoporotic animal models. Histological examination of the hind limb bone revealed that, similar to ALN, PTH inhibited the osteoclasts and sclerostin-positive cells. The mRNA levels of TNFα and IL-6 tended to decrease with ALN or PTH treatment compared with those without any treatment.
Treatment with PTH as well as BP prevented bone loss, mechanical hyperalgesia, osteoclast increase, and osteocyte increase. Similar to BP, the inhibitory effect of PTH on osteoclasts might contribute to the improvement of skeletal pain.
关于特立帕肽（甲状旁腺激素，PTH）与双膦酸盐（BP）在骨质疏松症疼痛相关行为和免疫组化结果方面的比较报道较少。本研究的目的是评估与骨质疏松症相关的骨骼疼痛，并研究PTH和BP对后肢去负荷（HU）小鼠疼痛和骨质流失的抑制作用。通过检查疼痛相关行为和免疫组化结果来评估HU小鼠骨质疏松性疼痛的机制。还评估了PTH和阿仑膦酸钠（ALN，一种有效的破骨细胞抑制剂）对这些参数的影响。
将8周龄雄性ddY小鼠尾部悬吊2周，并分为四组：仅接受尾部悬吊且注射赋形剂的后肢负重（HL）小鼠；接受尾部悬吊并注射赋形剂的HU小鼠；接受PTH治疗的HU小鼠；接受ALN治疗的HU小鼠。重新负重后立即皮下注射赋形剂、PTH或ALN。经过2周的治疗后，使用von Frey细丝检查机械敏感性。取出双侧后肢进行微型计算机断层扫描、免疫组化分析和信使核糖核酸（mRNA）表达分析。
尾部悬吊的HU小鼠出现骨质流失和后肢机械性痛觉过敏。HU小鼠后肢骨中的破骨细胞和硬化蛋白阳性细胞增加。此外，在骨质疏松动物模型中，PTH和ALN均能预防HU诱导的骨质流失和机械性痛觉过敏。后肢骨的组织学检查显示，与ALN相似，PTH可抑制破骨细胞和硬化蛋白阳性细胞。与未进行任何治疗相比，ALN或PTH治疗后肿瘤坏死因子α（TNFα）和白细胞介素6（IL-6）的mRNA水平有下降趋势。
PTH和BP治疗均可预防骨质流失、机械性痛觉过敏、破骨细胞增加和骨细胞增加。与BP相似，PTH对破骨细胞的抑制作用可能有助于改善骨骼疼痛。
