Effects of morning vs. evening teriparatide injection on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Michalská, Dana; Luchavova, M.; Zikán, Vı́t; Raška, Ivan; Kubêna, Aleŝ; Stepan, Jan J.

doi:10.1007/s00198-012-1955-4

Cited by 38 publications

(24 citation statements)

References 26 publications

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“…While PTH agents are widely used for osteoporosis, it has been reported that they enhance the early chondrogenic stages of endochondral bone formation 27 . A previous study on the effects of teriparatide administration in osteoporosis patients reported twice the increase in bone mineral density following a morning administration compared to an evening administration 28 , and our data (this study and our previous study 19 ) suggest that PTH directly changes the bone and cartilage circadian clock state. These indicate the possibility that circadian clock directly modulates PTH function of bone mineral density increase.…”

Section: Discussionsupporting

confidence: 75%

A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site

Kunimoto

Okubo

Minami

et al. 2016

Sci Rep

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The circadian clock contains clock genes including Bmal1 and Period2, and it maintains an interval rhythm of approximately 24 hours (the circadian rhythm) in various organs including growth plate and articular cartilage. As endochondral ossification is involved not only in growth plate but also in fracture healing, we investigated the circadian clock functions in fracture sites undergoing healing. Our fracture models using external fixation involved femurs of Period2::Luciferase knock-in mice which enables the monitoring of endogenous circadian clock state via bioluminescence. Organ culture was performed by collecting femurs, and fracture sites were observed using bioluminescence imaging systems. Clear bioluminescence rhythms of 24-hour intervals were revealed in fracture healing sites. When parathyroid hormone (PTH) was administered to fractured femurs in organ culture, peak time of Period2::Luciferase activity in fracture sites and growth plates changed, indicating that PTH-responsive circadian clock functions in the mouse femur fracture healing site. While PTH is widely used in treating osteoporosis, many studies have reported that it contributes to improvement of fracture healing. Future studies of the role of this local clock in wound healing may reveal a novel function of the circadian timing mechanism in skeletal cells.

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Section: Discussionsupporting

confidence: 75%

A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site

Kunimoto

Okubo

Minami

et al. 2016

Sci Rep

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“…In an investigation using DXA, Neer et al ([2001]) reported that a 40-µg dose of teriparatide decreased bone mineral density at the shaft of the radius by two more percentage points. Michalska et al ([2012]) investigated the efficacy of daily teriparatide at the distal 1/3 radius using DXA and reported a significant decrease in BMD of 2–3% at 6 months. Using the results of hr-pQCT, Macdonald et al ([2011]) reported that BMD of the distal radius decreased with daily teriparatide.…”

Section: Discussionmentioning

confidence: 99%

Once-weekly teriparatide increases bone mineral density in the distal 1/10 radius, but not in the distal 1/3 radius

et al. 2014

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Teriparatide significantly increases bone mineral density (BMD) of the lumbar vertebrae and femur and has a strong effect in reducing the risk of bone fractures. However, few detailed investigations with dual-energy X-ray absorptiometry (DXA) of the effects of teriparatide on the radius have been reported; specifically, there are no reports of the use of once-weekly teriparatide. In this study, the effect of once-weekly teriparatide in increasing BMD was examined in the distal 1/10 of the radius and the distal 1/3 of the radius using a DXA system for the radius. In addition, the effect of radius positioning, especially accurate correction of rotation and inclination before and after administration of teriparatide, was evaluated in an assessment of its efficacy. It was found that when positioning was corrected, a significant increase in BMD in the distal 1/10 of the radius was observed after 6 months of once-weekly teriparatide. In the distal 1/3 of the radius, no significant increase of BMD was observed. This suggests that when DXA scans of the radius are analyzed with appropriate positioning, weekly teriparatide significantly increases BMD in the distal 1/10 of the radius, which is rich in cancellous bone.

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“…Teriparatide (recombinant human PTH (1-34)) is a bone anabolic agent for treatment of patients with osteoporosis ( Augustine and Horwitz 2013 ). In osteoporosis patients, morning teriparatide treatment appears to function better than night-time administration, but the detailed biological mechanism is not fully understood ( Michalska et al 2012 ).…”

mentioning

confidence: 99%

Parathyroid hormone resets the cartilage circadian clock of the organ-cultured murine femur

Okubo¹,

Fujiwara²,

Minami³

et al. 2015

Acta Orthopaedica

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Background and purpose The circadian clock governs endogenous day-night variations. In bone, the metabolism and growth show diurnal rhythms. The circadian clock is based on a transcription-translation feedback loop composed of clock genes including Period2 (Per2), which encodes the protein period circadian protein homolog 2. Because plasma parathyroid hormone (PTH) levels show diurnal variation, we hypothesized that PTH could carry the time information to bone and cartilage. In this study, we analyzed the effect of PTH on the circadian clock of the femur.Patients and methods Per2::Luciferase (Per2::Luc) knock-in mice were used and their femurs were organ-cultured. The bioluminescence was measured using photomultiplier tube-based real-time bioluminescence monitoring equipment or real-time bioluminescence microscopic imaging devices. PTH or its vehicle was administered and the phase shifts were calculated. Immunohistochemistry was performed to detect PTH type 1 receptor (PTH1R) expression.Results Real-time bioluminescence monitoring revealed that PTH reset the circadian rhythm of the Per2::Luc activity in the femurs in an administration time-dependent and dose-dependent manner. Microscopic bioluminescence imaging revealed that Per2::Luc activity in the growth plate and the articular cartilage showed that the circadian rhythms and their phase shifts were induced by PTH. PTH1R was expressed in the growth plate cartilage.Interpretation In clinical practice, teriparatide (PTH (1-34)) treatment is widely used for osteoporosis. We found that PTH administration regulated the femoral circadian clock oscillation, particularly in the cartilage. Regulation of the local circadian clock by PTH may lead to a more effective treatment for not only osteoporosis but also endochondral ossification in bone growth and fracture repair.

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Effects of morning vs. evening teriparatide injection on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Abstract: 12-month morning administration of TPTD resulted in a larger increase in the lumbar spine BMD than the evening application. The timing of TPTD administration may be important for its efficacy.

Cited by 38 publications

References 26 publications

A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site

A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site

Once-weekly teriparatide increases bone mineral density in the distal 1/10 radius, but not in the distal 1/3 radius

Parathyroid hormone resets the cartilage circadian clock of the organ-cultured murine femur

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