Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
APNC, Gothenburg, Sweden.
JAMA Netw Open. 2024 Jun 3;7(6):e2415455. doi: 10.1001/jamanetworkopen.2024.15455.
Daily supplementation with the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) vs placebo has previously been demonstrated to reduce bone loss in an estrogen deficiency mice model and older women, although the magnitude of the effect was small. We hypothesized that long-term treatment with L reuteri could result in clinically relevant skeletal benefits in postmenopausal osteoporosis.
To evaluate whether daily supplementation with L reuteri vs placebo could reduce early postmenopausal bone loss and whether the effects remained or increased over time during 2 years of treatment.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, placebo-controlled clinical trial was conducted between December 4, 2019, and October 6, 2022, at a single center in Gothenburg, southwestern Sweden. Participants were recruited by online advertisements, and letters were sent to 10 062 women aged 50 to 60 years. Responding women (n = 752) underwent telephone screening, resulting in 292 women being invited to a screening visit. Of those who were screened, 239 women met all inclusion criteria and had no exclusion criteria.
Capsules with L reuteri in 2 doses, 5 × 108 (low dose) or 5 × 109 (high dose) colony-forming units, taken twice daily or placebo were administered. All capsules also included cholecalciferol, 200 IU.
The primary outcome was the relative change in tibia total volumetric bone mineral density (vBMD) over 2 years. Secondary outcomes included relative change in areal BMD of the lumbar spine and total hip, bone turnover markers C-terminal telopeptide cross-links of collagen type I and type I procollagen intact N-terminal propeptide, as well as tibia trabecular bone volume fraction and cortical vBMD. Both intention-to-treat and per-protocol analyses were conducted.
A total of 239 postmenopausal women (median age, 55 [IQR, 53-56] years) were included. Tibia vBMD (primary outcome), hip and spine vBMD, and tibia cortical area and BMD decreased significantly in all groups, with no group-to-group differences (percent change tibia vBMD high dose vs placebo least-squares means, -0.08 [95 CI, -0.85 to 0.69] and low dose vs placebo least-squares means, -0.22 [95% CI, -0.99 to 0.55]). There were no significant treatment effects on any other predefined outcomes. A prespecified sensitivity analysis found a significant interaction between body mass index (BMI) and treatment effect at 2 years. No significant adverse effects were observed.
In this randomized clinical trial of 239 early postmenopausal women, supplementation with L reuteri had no effect on bone loss or bone turnover over 2 years. The observed interaction between BMI and treatment effect warrants further investigation.
ClinicalTrials.gov Identifier: NCT04169789.
重要性：先前的研究表明，每日补充罗伊氏乳杆菌 ATCC PTA 6475（L 罗伊氏乳杆菌）益生菌可减少雌激素缺乏小鼠模型和老年女性的骨丢失，尽管其作用幅度较小。我们假设长期使用 L 罗伊氏乳杆菌可能会在绝经后骨质疏松症患者中产生具有临床意义的骨骼益处。
目的：评估每日补充 L 罗伊氏乳杆菌与安慰剂相比是否可以减少绝经早期的骨丢失，以及在 2 年的治疗期间，这种效果是否会随着时间的推移而持续或增加。
设计、地点和参与者：这是一项在瑞典西南部哥德堡的一个单一中心进行的双盲、随机、安慰剂对照临床试验。通过在线广告招募参与者，并向 50 至 60 岁的 10062 名女性发送信件。有回应的女性（n=752）接受了电话筛查，其中 292 名女性受邀参加了筛查访问。在接受筛查的女性中，有 239 名女性符合所有纳入标准且无排除标准。
干预措施：每天服用两次 L 罗伊氏乳杆菌胶囊，剂量为 5×108（低剂量）或 5×109（高剂量）菌落形成单位，或安慰剂。所有胶囊还包含 200 IU 的胆钙化醇。
主要结局和测量：主要结局是 2 年内胫骨总容积骨矿物质密度（vBMD）的相对变化。次要结局包括腰椎和全髋的面积骨密度、骨转换标志物 I 型胶原 C 端肽交联和 I 型前胶原完整 N 端肽、胫骨小梁骨体积分数和皮质 vBMD 的相对变化。均进行意向治疗和方案分析。
结果：共纳入 239 名绝经后女性（中位年龄 55[IQR，53-56]岁）。胫骨 vBMD（主要结局）、髋部和脊柱 vBMD 以及胫骨皮质面积和 BMD 在所有组中均显著下降，各组间无差异（高剂量组胫骨 vBMD 变化百分比与安慰剂最低平方均值差异，-0.08[95%CI，-0.85 至 0.69]；低剂量组胫骨 vBMD 变化百分比与安慰剂最低平方均值差异，-0.22[95%CI，-0.99 至 0.55]）。在任何其他预设结局上，均未观察到治疗效果的显著差异。一项预设的敏感性分析发现，2 年内 BMI 和治疗效果之间存在显著的交互作用。未观察到明显的不良反应。
结论和相关性：在这项针对 239 名早期绝经后女性的随机临床试验中，补充 L 罗伊氏乳杆菌对 2 年内的骨丢失或骨转换没有影响。观察到的 BMI 和治疗效果之间的交互作用值得进一步研究。
试验注册：ClinicalTrials.gov 标识符：NCT04169789。
