title: A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.
abstract: Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone formation at the endocortical surface.
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA. Electronic address: bjsmith@okstate.edu.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Smith
authors.forename: So Young
authors.initials: SY
authors.lastname: Bu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rendina
authors.forename: Yin F
authors.initials: YF
authors.lastname: Lim
authors.forename: Denver
authors.initials: D
authors.lastname: Marlow
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Clarke
authors.forename: Diane M
authors.initials: DM
authors.lastname: Cullen
authors.forename: Edralin A
authors.initials: EA
authors.lastname: Lucas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003720:Densitometry; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D027861:Prunus / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D010936:Plant Extracts
keywords: AIN; Alp; American Institute of Nutrition; BAP; BFR; BMD; BMP; BV/TV; Bone histomorphometry; Coll1a; Conn Density; DP; DPD; DXA; Dried plum; Estrogen; GI; HD; IGF-I; LD; MAR; MD; MS; Menopause; N-terminal propeptide of type I procollagen; Nfatc1; OPG; OVX; Osteoporosis; P1NP; PTH; Parathyroid hormone; Rankl; Runx2; SD; SHAM; SHAM operated; Sprague Dawley; TNF-α; TRAP; TbN; TbSp; TbTh; VOI; alkaline phosphatase; bone formation rate; bone mineral density; bone morphogenetic protein; bone volume per total volume; bone-specific alkaline phosphatase; connectivity density; deoxypyridinoline crosslinks; dried plum; dual-energy X-ray absorptiometry; gastrointestinal tract; high dose dried plum; insulin-like growth factor-I; low dose dried plum; medium dose dried plum; micro-computed tomography; mineral apposition rate; mineralizing surface; nuclear factor for activated T cells 1; osteoprotegerin; ovariectomized; parathyroid hormone; receptor activator for NF-kappa B ligand; runt-related transcription factor 2; tartrate resistant acid phosphatase; trabecular number; trabecular separation; trabecular thickness; tumor necrosis factor-alpha; type I collagen; volume of interest; μCT