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Table 3 Evidence on the skeletal effects of Ejiao formulations

From: Ejiao as a preventive agent for osteoporosis - a scoping review of current evidence

Researchers

Composition of prescription

Study Design

Findings

Xiong et al. (1999) [52]

Ejiao, Astragalus membranaceus, cooked Rehmannia glutinosa, Ostrea gigas

Animals: 20-d-old male Wistar rats

Disease model: bone loss induced by retinoic acid (70 mg/kg/day for 20 days)

Treatment: Calcium Ejiao oral solution (CCA) at 0.79, 1.58 and 2.37 g/kg/day, p.o., 6 weeks

Negative control: normal saline

Positive control: Longmu Zhuanggu granules (5 g/kg, p.o.)

Serum calcium level: ↑ vs. negative control

Serum phosphorus level: ↑ vs. negative control

Serum ALP level: ↓ vs. negative control

Femoral calcium and phosphorus content: ↑ vs. negative control

X-ray imaging: ↓ signs of bone loss (thinner cortical bone, reduced trabecular bone density) in treatment groups vs. negative control

Animals: 20-day-old male & female Wistar rats

Disease model: vitamin D deficiency-induced rickets model

Treatment: Oral calcium CCA at 0.79, 1.58 and 2.37 g/kg/day, p.o., 60 days

Negative control: normal saline

Positive control: Longmu Zhuanggu granules (5 g/kg, p.o.)

Negative control: NA

Serum calcium level: ↑ vs. negative control

Serum phosphorus level: NS

Serum ALP level: ↓ vs. negative control

Femoral calcium and phosphorus content: ↑ vs. negative control

X-ray imaging: ↓ signs of osteomalacia vs. negative control

Gu et al. (2019) [53]

Radix Rehmanniae Praeparata: Rehmannia glutinosa

Yam: Dioscorea opposita

Dodder: Cuscuta chinensis

Cornel: Cornus officinalis

Lycium: Lycium chinense

Eucommia: Eucommia ulmoides

Radix Angelicae Sinensis: Angelica sinensis

Cinnamon: Cinnamomum cassia

Processed Radix Aconiti Lateralis: Aconitum carmichaelii

Placenta: Placenta hominis

Ejiao: Asini Corii Colla

Radix Codonopsis: Codonopsis pilosula

Rhizoma Atractylodis Macrocephalae: Atractylodes macrocephala

Semen Coicis: Coix lacryma-jobi

Fructus Amomi: Amomum villosum

Baked tortoise’s shell: Testudinis Carapax et Plastrum

Antlers plastic: Cervi Cornu Pantotrichum

Animals: 4-month-old Female Wistar rats

Disease model: OVX-induced osteoporosis

Treatment: AOD 10 g/kg, p.o., 12 months

Negative control: normal saline

Positive control: Yougui Pill 10 g/kg, p.o.

BMD: ↑ vs. negative control

Histology: ↑ trabecular bone area vs. negative control

Serum PINP and β-CTX: ↓ vs. negative control

Skeletal ALP, BMP2, Runx2, collagen I, and osteopontin mRNA expression: ↑ vs. negative control

Jia et al. (2013) [55]

Ejiao

Yin Yang Huo: Epimedium sagittatum

Tu Si Zi: Cuscuta chinensis

Bu Guo Zi: Psoralea corylifolia

Huai Niu Xi: Achyranthes bidentata

Oyster: Ostrea gigas

Su Mu: Caesalpinia sappan

Animals: 8-month-old Sprague-Dawley rats

Disease Model: OVX - osteoporosis

Treatment:

Ejiao Kidney-Tonifying Bone Nourishing Formula (10 g/kg daily, p.o., 3 months)

Negative control: NA Positive control:

Alendronate sodium (8.2 mg/kg, p.o., weekly)

Body weight: ↑ vs. negative control

Uterus and kidney indices: ↑ vs. negative control

BMD: ↑ vs. negative control

Jia et al. (2013) [54]

Ejiao

Yin Yang Huo: Epimedium sagittatum

Tu Si Zi: Cuscuta chinensis

Bu Guo Zi: Psoralea corylifolia

Huai Niu Xi: Achyranthes bidentata

Oyster: Ostrea gigas

Su Mu: Caesalpinia sappan

Animals: 8-month-old Sprague-Dawley rats

Disease Model: OVX - osteoporosis

Treatment:

Experimental Groups:

Ejiao Kidney-Tonifying Bone Nourishing Formula (10 g/kg daily, p.o., 3 months)

Negative control: NA Positive control:

Alendronate sodium (8.2 mg/kg, p.o., weekly)

Body weight changes: ↑ vs. Control group

Uterus and kidney indices: ↑ vs. control group

Serum OCN and PICP levels: ↑ vs. Control group

Pan et al. (2023) [58]

Ejiao

Wolfberry: Lycium barbarum

Spatholobus: Spatholobus suberectus

Codonopsis: Codonopsis pilosula

Deer’s antler gelatin

Tuckahoe: Poria cocos

Mulberry: Morus alba

Cooked rehmannia: Rehmannia glutinosa

Achyranthes: Achyranthes bidentata

Red sage: Salvia miltiorrhiza

Wulingxian: Lindera aggregate

Tortoiseshell gum

Atractylodes macrocephala

Rheum palmatum

Shenji

Herba Epimedii

Licorice: Glycyrrhiza uralensis

Patients: 120 patients with OVCF treated with PVP

Treatment group:

35 men and 25 women

Mean age: 66.27 ± 2.15 years old

Treatment: Ejiao paste (10 g, p.o., 2 times/day) + Baduanjin exercise

Positive control group:

33 men and 27 women

Mean age: 66.18 ± 2.20 years old

Control: Calcium carbonate (1.25 g) + Vitamin D3 (200 IU) + guidance (consume 1.20–1.40 g/kg of high-quality protein daily, engage in walking exercises for over 30 min, and get regular sun exposure

Duration: 6 months

Follow-Up: 3 years

Negative control: NA

BMD: ↑ vs. positive control

AVBH: ↑ vs. control

Serum B-Cross I: N-MID Ost, PTH, ↓ vs. control

Functional improvement: ↑ vs. control

Jia et al. (2018) [59]

Ejiao, Ostrea gigas

Patients: 80 children with Vitamin D-deficiency-induced rickets

Treatment group:

n = 40 children (23 males and 17 females)

Mean age: 15.3 ± 5.3 month

Treatment: Ejiao-Mu Li Oral Solution (≤ 6 months: 10 mL daily, thrice a day; > 6 months: 10 mL/day, twice a day) combined with zinc-iron-calcium composite preparation (10 mL, 3 times a day) for 12 weeks

Positive control:

n = 40 children (21 males and 19 females)

Mean age: 14.7 ± 5.3 month

Treatment: Zinc-iron-calcium composite preparation (10 mL, 3 times a day) for 12 weeks

*Both groups received intramuscular vitamin D 300,000 IU, followed by 4-week oral vitamin D drops for 8 weeks (< 1 year: 500 IU/day, ≥ 1 year: 700 IU/day)

Total effective rate: ↑ vs. positive control

Bone metabolism indicators:

ALP↑ vs. positive control

Bone density (radius, ulna) and 25-(OH) D3 levels: ↑ vs. positive control

Chen et al. (2014) [60]

Ejiao: Colla Corii Asini

Jujube: Ziziphus jujuba

Goji Berry: Lycium barbarum

Astragalus: Astragalus membranaceus

Curculigo: Curculigo orchioides

Amomum: Amomum villosum

Participants: 73 patients with closed bone fractures

Treatment group:

n = 37 patients

Mean age: 46.21 ± 6.24 years old

Treatment: Ejiao and Astragalus, 10 mL, p.o., twice daily, alongside a self-made bone healing ointment applied 6–9 times daily for one week

Positive control:

n = 36 patients

Mean age: 45.93 ± 5.71 years old

Treatment: Calcium gluconate oral solution (600 mg/d)

Negative control: NA

Total effective rate: ↑ vs. positive control

Healing outcomes after 12 weeks: ↑ vs. positive control

  1. Abbreviations: 25-(OH) D3, 25-hydroxyvitamin D3; β-CTX: β-C-terminal telopeptide of type I collagen; ALP, Alkaline phosphatase; AVBH, Anterior vertebral height; BMD, Bone mineral density; BMP2, Bone morphogenetic protein 2; NA, Not available; N-MID Ost, n-terminal middle osteocalcin; NS, Not significant; OCN, Osteocalcin; OVX, Ovariectomised; PICP, Procollagen type I C-terminal propeptide; PINP, N-terminal propeptide of type I procollagen; p.o., per-oral; PTH, Parathyroid hormone; PVP, Percutaneous vertebroplasty; Runx2, Runt-related transcription factor 2; ↑, increase or upregulate;↓, decrease or downregulate