Therapy for Inhibition of Bone Resorption
Therapy for Inhibition of Bone Resorption and Promotion of Bone Formation
William Smith-Mensah & M.D. Mario Cerame M.D.
Introduction: The purpose of this study was to evaluate the efficacy of organic compound-based bone forming materials in slowing bone resorption and invariably to facilitate bone formation in postmenopausal women. A bio-pharmaceutical source of calcium, proteins, and bio-balanced profile of minerals was used in this study. This compound (OstiGen - U.S. Foods & Pharmaceuticals, Inc., Madison, WI) contained the essential components to promote normal bone resorption and formation and was ideal for use in conducting this evaluation.
Subjects and Methods: Thirteen healthy and normal menopausal and postmenopausal women were selected ranging in ages from forty to seventy-one. All subjects did not take any dietary supplements, and were on an otherwise normal balanced diet. The study was conducted over a 12 week period during which time all subjects were administered two grams of Product A, the main ingredient in OstiGen, in liquid-dissolving powder form, dissolved in four ounces of water twice daily. The rate of bone resorption was measured using the Urine NTx Assay (Osteomark, Princeton, NJ). The urine NTx assay is a quantitative measurement of the crosslinked N-teleopeptides of bone type-I collagen. A quantitative measure of the NTx level in the urine correlates directly to bone resorption. The presence of NTx molecules above the normal value (38nMBCE) in urine is indicative of bone loss. Baseline NTx testing was administered to the subjects prior to the initiation of Product A therapy.
Results: All thirteen subjects had elevated baseline NTx readings ranging from forty-three to seventy-three nMBCE (nanomoles per bone collagen equivalents). After twelve weeks of therapy, all the subjects reached a normal reading of 38nMBCE, which is an indication that OstiGen suppressed abnormal bone resorption and that bone resorption was equivalent to bone formation.
Conclusion: The use of OstiGen over time inhibits abnormal bone resorption, and aids in building and maintaining healthy, bone structure.
Bone is an active body system, which is in constant equilibrium between formation (osteroblastic activity) and resorption, or loss (osteoclatic activity). Osteoporosis is a condition where there is a shift toward increased bone resorption, resulting in a net bone loss, making the bone more fragile and prone to breakage. Osteoporosis, with its precursor condition of bone loss, is a serious healthcare issue that affects 44 million Americans. Many more including young persons are at risk of osteoporosis (1-4). Recent research into the biochemistry of bone formation and the suppression of bone resorption has led to the development of new therapies and programs for the prevention and treatment of bone loss and osteoporosis. Organic compounds from natural sources contain the best-known sources of nutrients for healthy bone growth in young persons and maintenance of bone in the adult populations (5-7). In addition to dietary calcium, the organic compound contains a balanced bio-available mineral profile, bone morphogenic proteins (BMP), carbohydrates and essential fatty acids for the growth, development and maintenance of bones, teeth and skeletal structures (8, 9). Organic compound proteins have been shown to promote bone formation and slow excess bone resorption (8, 10, 11).
Calcium supplements alone are not adequate for quality bone formation (12, 13, 31). Recent developments in bone science recognize a need for other bone mineral nutrients as well as proteins to work in conjunction with certain hormones for healthy bone formation and maintenance (14-16).
U.S. Foods and Pharmaceuticals (USFP) Inc., has developed OstiGen, a new therapeutic formulation containing the USFP–patented organic compound, containing a unique combination of two forms of high quality dietary calcium. Product A includes minerals with high bio-availability, proteins. These proteins have been shown to stimulate bone growth and slow down bone resorption (10, 11, 15, 17- 20). Product A has the same mineral profile (proportions and content) as bone (Table 1) and provides these organic precursors and inorganic components necessary for the manufacture and maintenance of bone in powder form.
TABLE 1. MINERAL ANALYSIS OF COMPOUND A. COMPARED WITH BONE
URINE NTX (A BONE RESORPTION MARKER)
Urine NTx is a method examining cross-linked N-telopeptides of type-I collagen (NTx) that the body excretes in urine when bones are broken down (21, 22). An increased rate of NTx excretion indicates a higher rate of osteoclast activity and bone destruction. Unlike bone mineral density (BMD) measurements, which typically detect changes in bone density over years (23), NTx is able to detect changes in bone metabolism in weeks or months (24). Two possible applications of NTx are to (a) predict bone loss in peri- and postmenopausal women and to (b) monitor the skeletal response to treatment. While NTx testing does not directly determine osteoporosis, it does determine the likelihood of decreasing bone density, as measured by conventional bone mass measurements. The higher the rate of bone resorption as measured by NTx, the greater the rate of bone loss (22, 25) Elevated levels of bone resorption (NTx) markers found in urine are associated with higher rates of bone loss in postmenopausal women (26, 27).
Bone resorption markers may also play a role in evaluating the effects of therapy (28). Current osteoporosis treatments act to decrease bone resorption, which is detectable by changes in NTx studies (21). Using markers, the efficacy of treatment may be determined in a matter of months. These shortened timelines for treatment increase feedback response by comparison to changes in bone density that may not be detected for one or two years. Experts suggest that demonstrating an early evidence that the osteoporosis regimen may be working can reinforce a patient’s desire to continue therapy, enhancing compliance with treatment. Many specialists treating osteoporotic patients use bone resorptive markers in assessing the role of high bone turnover in pathogenesis and prognosis, as well as assessing the response to antiresorptive drugs. Failure to detect a decrease in bone markers could indicate a lack of compliance or efficacy of antiresorptive drug therapy.
GOAL OF STUDY
OstiGen, an organic-based therapeutic formulation, contains essential bone morphogenic proteins and other factors capable of promoting bone formation and inhibiting bone resorption. From the standpoint of osteoporosis therapy, this study investigated the efficacy of OstiGen in slowing bone resorption and inferring the stimulation of bone formation.
SUBJECTS AND METHODS
Subjects. Participants were menopausal and postmenopausal women recruited from the population at large in the Madison, Wisconsin area who were otherwise healthy, not taking any diet supplements and living normal lives. Seventeen women initially signed the consent forms for the study but four were disqualified for non-compliance of the protocol. Thirteen women with ages ranging from forty to seventy-one completed the twelve-week study. The study protocol complied with HIPAA regulations.
Protocol. After enrollment, each participant was given a urine NTx assay kit with instructions to collect the second void of morning urine sample (pre-treatment) and mail the sample with the return overnight mail to the central testing laboratory (Women’s Health America, Madison, WI) to establish baseline NTx readings. Participants were notified of their initial readings. Normal NTx readings are below thirty-eight nMBCE, an elevated NTx is between forty to sixty nMBCE and a high NTx is above sixty nMBCE. An elevated NTx is indicative of osteopenia while a high NTx is inferred as osteoporosis in correlating to low BMD and bone loss. Selected participants, with NTx readings higher than thirty eight were mailed Product A powder individually packaged in two gram packets for a twelve week supply along with use instructions, daily intake recording calendars, second test NTx kits and other necessary contact information. Participants were required to consume two grams of Product A powder (500mg calcium equivalent) two times daily, totaling one thousand mgs of calcium equivalent, two times daily, in the morning and one-half hour before bed-time. Participants had unlimited access to information with study monitors. Participants were contacted every week to verify that they were in compliance with the study protocols, maintaining expected records and assessments were made about how well the product was being tolerated. After twelve weeks of Product A intake, the participants who were verified to have been in compliance with the protocol were requested to send a second urine sample (post-treatment) by overnight mail.
|Table 2: Demographics of Subjects
|Total number of subjects
|Number of pre-menopausal subjects
|Number of postmenopausal subjects
|Average age of subjects
|Average pre-treatment NTx of all subjects
|Average pre-treatment NTx of pre-menopausal subjects
|Average pre-treatment NTx of postmenopausal subjects
Status of subjects. During the twelve-week study period, none of the subjects reported bloating, diarrhea, heartburn, allergy symptoms or adverse reactions from the use of the Product A powder. They all maintained their normal health with routine living. None reported to face adverse conditions in life, none of the subjects were involved or reported to have been in any accident, no allergies of any kind or any treatment for any diagnosis of diseases.
Table 3: NTx reading AND Table 3a: Graphs
In this study, bone resorption or bone breakdown was measured using the urine NTx assay (Osteomark, Princeton, NJ). NTx levels were assessed before treatment (baseline) and after twelve weeks of treatment (final). The mean pre-menopausal score or NTx bone resorption is 38nMBCE.
Table 3/3a presents the data on bone resorption changes at twelve weeks compared to baseline. Eleven out of thirteen subjects had baseline NTx readings from 43 to 60 (‘Elevated NTx Group’) and the other two subjects had baseline readings above 60 (‘High NTx Group’). The subjects in the high NTx baseline group were ages seventy and seventy-one respectively, while the elevated NTx baseline group ranged from ages forty to sixty-nine. All thirteen subjects experienced a reduction in NTx marker of bone resorption. Twelve out of thirteen subjects had a final NTx reading of 37 or 38 (pre-menopausal mean), however, one subject had a final NTx score of 33. Percentage change of baseline for the subjects ranged from -47.94% to -13.63% with the most reduction noted with the subjects in the high NTx baseline group.
Osteoporosis is a disease involving a pathologic bone remodeling process resulting in a shift toward increased osteoclastic activity and decreased osteroblastic activity leading to a net bone loss, resulting in an increased risk of fractures (1, 28-30). This phenomenon normally occurs in women during and following menopause. Such bone resorption is seen with excretion of NTx in urine and can easily be measured to observe and modify treatement. In the study, baseline urine NTx measurements above 38 nMBCE were indicative of abnormal bone resorption with a subset of the group in the ‘High NTx’ category i.e. the group at a relatively higher risk of fractures.
Bone remodeling is a complex process dictated by both organic and inorganic factors. The deficiency of these factors over a period of time leads to abnormal bone resorption and eventual bone loss (28). OstiGen, with its main ingredient (Product A), contains both organic and inorganic components, which serve as “raw materials” for building and maintaining bone. The inorganic components are precursors of calcium hydroxyapatite (see Table 1). Several studies have shown that proteins in complex with other nutrients including minerals and vitamins promote bone formation (10, 11, 17, 18 ).
The subjects in the study, after treatment with OstiGen for twelve weeks, showed a reduction in urine NTx levels to the premenopausal mean of 38nMBCE, which is an indication that their bone resorption at the end of the study was equivalent to bone formation. Baseline at38 nMBCE 30nMBCE/creatinine. One of the subjects had an NTx reading of 33nMBCE, a value much lower than the pre-menopausal mean. This may be attributed to a phenomenon called ‘bone turnover suppression’. The highest percentage changes of baseline were seen with the older subjects (ages 69 to 71 years) recording a range from –36.66% to –47.94%. This subset with the highest relative NTx values had the most benefit granted during this study.
Direct measurement of the rate of bone loss in a patient with osteoporosis would require at least two measurements of bone mass over a 2-4 year interval (23). Such a strategy is not practical where it is necessary to decide whether or not to treat at the time of initial assessment. Since the rate of bone loss is proportional to the rate of bone turnover in postmenopausal women, it has been suggested that the rate of loss can be predicted by assessing bone turnover that are specific for bone resorption (23). Although rates of loss assessed in this manner are less accurate than rates of loss assessed over many years by sequential bone mineral density (BMD) measurements, a high rate of bone resorption above the premenopausal mean is associated with a 2-fold increase risk of vertebral and hip fracture independently of the prevailing BMD (23). Even though the study revealed the resolution of abnormal bone resorption to premenopausal levels with the use of OstiGen indicating that the presumed on-going bone resorption/bone loss was reversed, a concomitant study assessing BMD over a longer period is needed and has been planned for the future.
CONCLUSIONThe use of OstiGen over a twelve-week period by menopausal and postmenopausal subjects showed a decreased level of bone resorption. The group at the most risk for fractures had the greatest benefit in achieving a decrease to normal bone resorption levels. The subjects at relatively minimal risk for fractures also benefitted with delayed bone loss. The continued use of OstiGen, containing bone building precursors, appears to slow bone loss and shows great promise in helping to build bone which over time will be evident on BMD measurements.
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William Smith-Mensah M.D., Surgeon - Paul B. Hall Regional Medical Center, Paintsville, KY
Mario Cerame M.D., Surgeon - Lexington Surgical Associates, Chapel Hill, NC