New Paradigm for Addressing Bone Health Through Osteoinduction

January 04, 2019

When we are looking at healthy bone growth and effective remodeling, we know it requires homeostasis between osteoclasts and osteoblasts. This equilibrium facilitates bone resorption, and osteoblastic activity, which elicits osteogenesis (bone creation) [1] leading to overall bone health.

In conditions involving bone decline, pathological bone resorption or diminished osteogenesis can contribute to the onset of this condition. Also, estrogen deficiency (most notably after menopause and in some cases before) is known to play a prime role in bone loss. Other contributing factors for bone degradation may include vitamin D and calcium deficiencies and parathyroid disease (specifically secondary hyperparathyroidism) [1]. Furthermore, research shows that the development of low bone mineral density [BMD] can be attributed to the pathological changes in the differentiation of stem cell (SC) progenitors into osteoblasts (bone forming cells). Important risk factors for bone decline include advancing age, gender (female), low body weight, ethnicity (Caucasian and Asian), family history, and smoking. As a result, bone decline is a leading cause of fragility fractures, especially of the spine (vertebral compression) and hip [1, 2]. The differentiation of SC progenitors into osteoblasts is regulated by bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-ß (TGF-ß) protein superfamily. TGF-ß was the first local bone growth factor to be homogeneously purified. BMPs were first identified in the 1960s and over 20 members of this family have been identified and characterized [2]. In addition, growth factors such as basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), and vascular endothelial  growth factor (VEGF) support the maturation of nascent osteoblasts [3–10]. This protein signaling pathway is referred to as osteoinduction and it propagates bone and cartilage matrix synthesis (tissue) through osteoblast and chondrocyte differentiation, which subsequently promotes de novo bone growth and the formation of cartilage [1]. Inhibition of BMP-2, 4, 6, and 9 has been shown to inhibit osteogenic differentiation of osteoblasts, which resulted in net bone loss. 

Ostinol™, a novel dietary supplement, is powered by Cyplexinol®, the only protein complex comprised of BMPs and the active growth factors TGF-ß, bFGF, VEGF, and IGF (naturally bound to a specialized form of collagen in their natural physiologic levels). This protein complex has been proven, since its discovery in 1965, to be an osteoinductive complex capable of helping to stimulate the formation of de novo bone and cartilage.*

Animal models have previously shown that a protocol of a single BMP promotes a significant increase in bone markers [11–13]. Research involving the administration of BMP-6, to ovarectomized rats, has demonstrated an increase in bone volume of 78% and the simultaneous suppression of bone resorption [11]. Most of these studies, using a synthetic, singular protein, (administered intravenously and has a vastly different molecular composition from Cyplexinol®) revealed increases in bone markers such as BMD, bone tissue deposition, and mineralization.

Cyplexinol® is unique in that it is the only complex which consists of biologically active growth factors and BMPs. These active ligands are naturally bound to a specialized collagen, which protects the active proteins and ensures their delivery to receptors in the GI mucosa where they confer their osteoinductive activity.* This osteoinductive capability makes Cyplexinol® unique from other collagen products as well as other bone support supplements.*

For example, collagen preparations are fully hydrolyzed products which degrade the BMPs and growth factors, leaving collagen peptides that cannot elicit an osteoinductive response nor grow new bone and cartilage tissue [11, 14].*

Similarly, when comparing the BMP moieties within Cyplexinol® to other supplements such as milk basic protein (MBP) or protomorphogens (PMGs), neither of these substances are osteoinductive.* The dairy cow was domesticated in 4000 BC. Ever since, milk has been a key contributor to human health. It is recommended for bone health because it is an excellent source of calcium (a major constituent of bone). Milk also contains other compounds found to be effective for bone health [15]. Milk whey protein, a byproduct of the process of making cheese, is one of those compounds and is thought to have a direct effect on bone metabolism.* Previous in vitro and in vivo studies have shown that milk whey protein, specifically its basic protein fraction called milk basic protein (MBP), promotes osteogenesis and suppresses bone resorption [16–20].* A clinical trial following 33 healthy women for 6 months reported BMD gains for those women administered MBP [21], but additional clinical evidence is limited, leaving questions about clinical relevance.*

PMGs are characterized as the mineral skeleton on which the “nucleoprotein” (nucleic acid and ribose sugar) is bound. The concept of PMGs was put forth in 1947 with the publication of the book Protomorphology: The Principles of Cell Auto-regulation, which was co-authored by the scientists William Hanson and Royal Lee. Hanson and Lee felt PMGs were necessary to control the metabolism, growth, and repair of all living tissue (including bone). Today, we understand this mineral skeleton to refer to the phosphodiester backbone of DNA, which, while it may provide some cellular nourishment, is not osteoinductive [22]. Currently there are no randomized controlled trials (RCTs) investigating the efficacy and safety of PMGs for bone health.

Since 1965 when the first BMP complex was discovered, it has proven to be the only osteoinductive omplex.* In the late 1980s, this BMP complex was first extracted from human donor bone for surgical use in spinal fusion and comminuted fractures, which launched the field of osteobiologics. Some of the scientists and managers who helped pioneer that surgical product comprise ZyCal Bioceuticals’ expertise, now extracting this BMP complex (Cyplexinol®) from an ultra-pure food source—certified organic, closed-herd bovine bone. Ostinol™, powered by Cyplexinol® is providing healthcare practitioners with an unparalleled level of scientific evidence/clinical trials and ushering in a paradigm shift in the natural bone and joint supplement market with the only osteoinductive products [23, 24].*

“This osteoinductive capability makes Cyplexinol® unique from other collagen products as well as other bone products”

Dr. Jacquel Patterson is a licensed Naturopathic Doctor, completing her studies at the University of Bridgeport College of Naturopathic Medicine. She completed over 1,300 clinical hours at several naturopathic private practices and UB's Clinic, which serves a diverse patient population, prior to obtaining my license. She interned at Yale-Griffin Prevention Research Center and received UBCNM's distinguished Service Award. She also has an undergraduate degree from Cornell University in Applied Economics and Management, with a focus on the Food Industry and a MBA in Healthcare Management from Quinnipiac University. She is the current president of the American Association of Naturopathic Physicians.

 

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