Вы находитесь на странице: 1из 7

[Orthopaedics Today (2002): (IV), 3, 195-199]

The Efficacy of OST-6, A Polyherbal Formulation in the Management of


Primary Osteoporosis : A Pilot Study
Krishna Reddy, MS (Ortho)
Professor of Orthopedics, Kempe Gowda Institute of Medical Sciences Hospital & Research Centre
K.R.Road, V.V. Puram, Bangalore, India
and
Kala Suhas Kulkarni, MD
Medical Advisor, R&D Center, The Himalaya Drug Company, Makali, Bangalore, India

ABSTRACT
This was an open clinical trial carried out to investigate the effect of an herbal preparation OST-6
on bone loss in primary osteoporotic patients. Fifty patients (13 male and 37 female) aged between
40-80 years, with clinical symptoms of osteoporosis such as low back pain were included in the
study. After confirming the measurement of bone mineral density, at right heel, patients diagnosed
with either osteoporosis or osteopenia were included in the study. Among them, 6 male and 13
female patients had osteopenia, and 7 male and 24 female patients had osteoporosis. Additional
measures also included the estimation of serum calcium and phosphorous levels. All the patients
were administered OST-6 at a dose of 2 tablets, twice daily for 6 months. In this trial, all the
patients served as self-control. Symptom relief and bone densitometry was evaluated before and
after treatment. Results indicated that after 6 months, there was an increase in bone mineral
content by 1%. The bone loss in male patients when compared to healthy young adults of 25 years
was 36.83% pre-treatment and 35.83% post-treatment. When matched for age, it was 20.75% and
19.58% at pre- and post-treatment respectively. In female patients, bone loss when compared to a
young adult decreased from 25.27% to 24.61% and when matched for age, decreased from 12.51%
to 11.86%. The ‘T’ score decreased by –0.06 in males and –0.12 in females. Serum calcium
increased by 3% and serum phosphorous decreased by 3%. Biochemical parameters were within
the normal limits before and after treatment, thereby indicating that OST-6 can be safely
recommended for management of osteoporosis.

INTRODUCTION
Osteoporosis is a major public health problem and has been increasingly recognized that
maximizing peak bone mass at skeletal maturity may provide important protection against risk of
fracture in later life. Ninety to ninety five percent of total body peak bone mass is attained by the
end of the second decade1,2, with bone growth in adolescence accounting for about half of this
figure.3 Peak bone mass is determined by a combination of endogenous (genetic, hormonal) and
exogenous (nutritional, physical activity) factors.4 These exogenous factors are amenable to
intervention and could thus provide a base for public health strategies for preventing osteoporosis.

The aetiology of osteoporosis is multifactorial and its characteristic features are uncoupling of the
osteoblastic and osteoclastic processes of bone turnover and bone loss in adults. Approximately 3%
of cortical bone is replaced each year and approximately 25 % of trabecular bone is reabsorbed and
replaced every year.5 The trabecular bone has high surface-to-volume ratio and 70-85 % of the
surface of the bone is in contact with bone marrow. After the mid thirties, there is 0.3 to 0.5 % bone
loss per year. In early osteoporosis, there will be bone loss of 2-3 % per year and it mostly occurs in
cancellous bone. The total bone loss at a later stage may exceed 30-40%. After 50 years, there will
be a 40% chance of developing osteoporotic fracture during a person’s remaining lifetime.5

A specific cause of osteoporosis in most women is a rapid increase in bone loss after menopause,
primarily due to loss of estrogen. However, whenever estrogen is taken, the patients should be
cautioned about the development of breast cancer. Another fact is that not all postmenopausal
women who have lost estrogen develop postmenopausal osteoporosis. A weaker association was
found between calcium intake during adulthood and bone mass.6 Some women with very low
calcium intakes do not develop osteoporosis. Treatment with Vitamin-D and calcium supplements
will prevent some degree of loss of skeleton and decrease the likelihood of fractures. Calcium and
calcitonin supplements act by decreasing bone resorption. Calcium acts mainly by decreasing
activation of new bone remodeling units (not by decreasing action of existing osteoclasts).
Postmenopausal women who are not treated with estrogen require about 1,500 mg daily for calcium
balance. High dietary calcium suppresses age-related bone loss and reduces fracture rate in patients
with osteoporosis. Calcitonin has recently shown to be an effective agent in management of patients
with osteoporosis, but the drug is expensive and difficult to administer.

The ancient system of Indian medicine mentions several plants that are used to heal fractures and
cure many bone metabolic disorders. Ayurvedic preparations contain natural forms of calcium,
which prevent development of fractures in osteoporosis. One such preparation known as OST-6
consisting of Terminalia arjuna, which has been extensively used in the treatment of many
osteodystrophic conditions7, Withania somnifera, a rejuvenator that helps in relieving pain
associated with osteodystrophic conditions and is also useful in people with general debility,
nervous problems and muscular pain8. Commiphora wightii, increases the mineralization of the
bones9. Sida cordifolia contains phytosterol and potent phytoestrogens. Vanda roxburghii has anti-
inflammatory activity, which is useful for relief of bony pains of osteoporosis. Godanti bhasma and
Kukkutandatvak bhasma are the rich natural sources of calcium. The calcium present in this
formulation is extracted in a traditional way that can be easily absorbed in the intestines.10
Experimental evaluation of OST-6 in animal models showed inhibition of bone reabsorption. It also
stimulated new bone formation, thereby proving that it has a potential to be used as an anti-
osteoporotic agent.11 This study was planned to evaluate OST-6 in increasing the serum calcium
levels. The patients’ bone density was also indirectly assessed by ultrasound bone densitometry to
evaluate if OST-6 increases the bone mineral content by measuring the bone loss. Since this was a
pilot study involving a small group of patients and also to minimize the fracture risk, there was no
control group. The protocol, which included the research methodology, investigators brochures and
the patients’ consent forms was approved by the ethics committee of Kempe Gowda Institute of
Medical Sciences Hospital and Research Centre, Bangalore, India.

MATERIALS AND METHODS


Fifty patients (13 male and 37 female) aged between 30-80 years, with clinical symptoms of
osteoporosis such as low back pain were included in the study. After confirming the measurement
of bone mineral density, at right heel, the patients were confirmed as either osteoporosis or
osteopenia were included in the study. Among them, 6 male patients had osteopenia and 7 patients
had osteoporosis. Thirteen female patients had osteopenia and 24 patients had osteoporosis. The
exclusion criteria included pregnant women, evidence of malignancy, hyperthyroidism,
hypogonadism, and patients receiving long-term corticosteroids, methotrexate and heparin. All
patients were subjected to bone densitometry using lunar calcaneum bone densitometry and were
included only if they had more than 10% bone loss when compared to others of their age group and
/ or to a young adult of 25 years. Complete hematological and biochemical investigations were done
including serum calcium and phosphorous.

Bone Densitometry Instrument:


New methods of measuring osteoporosis using ultrasound have also been developed. One such
ultrasound system measures the fracture risk and also measures the percentage of bone mineral
density loss for that particular age when compared to a young adult. The measurement is done using
the calcaneum bone and takes about a minute. This instrument is useful as a screening test since it is
simple and inexpensive and it has good reproducibility (1-3%). As bone density of the calcaneum
reflects total body calcium, any thickening in the calcaneum may be used to predict fractures at
other sites. These ultrasound systems for testing osteoporosis are smaller and less expensive than
traditional DEXA systems. These systems have recently received US Food and Drug
Administration (FDA) clearance for its use in diagnosing osteoporosis. The instrument used in this
study is LUNAR ACHILLES PLUS DENSITOMETER QUS manufactured by General Electricals
Medical Equipment, Bangalore, India. This instrument measures the stiffness, which is a clinical
index developed by the Lunar Company and is a combination of BUA (Broad base Ultrasound
Attenuation) and SOS (Speed of Sound). It also measures the bone loss for the corresponding age
when compared to a healthy young adult of 25 years of the same sex. The T-Score, which is the
standard deviation (SD) when compared to a 25-year-old young healthy individual of the same sex
and the Z-Score is the SD for that corresponding age. These measurements were done using the
right heel of the patients. The fragile fracture risk directly corresponds to the bone mineral density.

All the patients were recommended OST-6 at a dose of 2 tablets, twice daily for six months. These
patients did not receive any supplementary calcium. The calcium content of OST-6 was measured
and analyzed as 250 mg of calcium per tablet. Hence, the total calcium administered to the patient
was 1000 mg/day. They were evaluated every month for improvement in the symptoms. At the end
of 6 months, the patients underwent complete hematological and biochemical analysis, with bone
densitometry. All these patients served as the self-control, because the efficacy of OST-6 was
evaluated on symptomatology and calcaneous bone density after the treatment.

Statistical Analysis
The statistical analysis was done using repeated ANOVA measures using Graph Pad Prism 3.0
software.

RESULTS
Forty nine patients completed the 6 month study. One male patient was lost for follow up. The
patients on being clinically evaluated showed an improvement in the symptoms from the first month
onwards. The serum calcium, which was 9.24 ± 0.53, improved to 9.54 ± 0.54, which showed a 3%
improvement during the 6 month study (p<0.0001). However, the drug was continued in these
patients till the bone mineral Table : Hematological and Biochemical Parameters
content was within normal limits. Creati- Alk.
The phosphorous content, which Hb TC Urea SGOT SGPT
nine Phos.
(gm%) (/cu.mm) (mg/dl) (IU/L) (IU/L)
was increased to 3.8 ± 0.53 due to (mg/dl) (IU/L)
osteoporotic changes, reduced to 3.5 Before 15.71 7611 22.47 0.83 18.14 9.28 69.22
treatment ± 0.85 ± 854.8 ± 4.61 ± 0.09 ± 1.94 ± 0.64 ± 6.58
± 0.51 after treatment, which
After 15.68 7688 22.14 0.83 19.71 9.40 57.33
displayed a 3% decrease within a treatment ± 0.72 ± 892.0 ± 3.86 ± 0.09 ± 1.77 ± 0.72 ± 6.42
span of 6 months (p<0.0001) (Fig.
1). In the male patients, the bone Fig. 1. Effect of OST-6 on Serum Calcium and Phosphorus
density when compared to young
adults increased by 1% and the bone
density, when matched to age,
increased by 1.17% (p<0.0001). The
T score which was -3.27 ± 0.79
reduced to – 3.21 ± 0.98 (p<0.0001).
The bone loss decreased from 36.83
± 11.68 to 35.83 ± 12.58 in 6 months
(p<0.0001). Among female patients,
the bone density when compared to a
young adult female, also increased
by 0.66% and the bone density, when
Fig. 2. Effect of OST-6 on T-score
matched to age, increased by 0.65%
(p<0.0001). The T score, which was
–2.33 ± 1.33 reduced to – 2.21 ±
1.41 (p<0.04932) (Fig. 2). The bone
loss decreased from 26.22 ± 13.20 to
25.22 ± 13.38 in just 6 months
(p<0.0001) (Fig. 3). Hematological
and biochemical parameters showed
no difference before and after
treatment (Table). This proves that
OST-6 is a safe herbal preparation
for use in patients with primary
Fig. 3: Effect of OST-6 on bone loss
osteoporosis.

DISCUSSION
Osteoporosis is characterized by low
bone mass and disruption of bone
architecture resulting in reduced
bone strength and increased risk of
fracture.12 After the attainment of
peak bone mass, bone loss in women
begins, at or shortly before,
menopause, in the spine and possibly
as early as the mid-30s in the
femoral neck. Bone mass is a major determinant of bone strength, and prospective studies have
shown an increasing gradient risk of fracture with decreasing bone density, a decrease in the latter
of 1 SD being associated with a 1.5-fold to 3.0-fold increase in risk of fracture.13-16 The strength of
this relation is similar to that between blood pressure and stroke and is equivalent to an eightfold to
12-fold difference in risk of fracture across the four quartiles of the distribution of bone density.
Though measurement of bone mass at any of the skeletal sites commonly assessed is of value in
defining risk of fracture, there is evidence that measurement of the site of potential fracture may
provide the best prediction, at least in the case of fracture of the hip.17,18

Bone fractures are an important cause of morbidity and mortality among the elderly even in western
countries.19 The annual occurrence of osteoporotic bone fractures is estimated at 1.3 million.20
Although a large majority of these occur among women, fracture rates among men are not trivial.
For example, men at age 50 have a 5% lifetime risk of sustaining a hip fracture.21 A low calcium
intake has been postulated to be an important predictor of fractures because bones are largely
composed of calcium phosphate and a combination of calcium phosphate and calcium hydroxide
called hydroxyapatite. There is evidence of an association between dietary calcium intake and peak
bone density,22-25 and conversely, calcium deficiency can lead to osteoporosis as a result of
continued calcium loss through feces and urine.26

Type I (“Postmenopausal”) osteoporosis is due to loss of estrogen, which affects postmenopausal


women. There is 2-3% accelerated loss for 6-10 years, which then returns to basal loss of 0.3-0.5 %
per year. There is primarily loss of trabecular bone. It is associated with greater decline in
medullary bone with preservation of cortical bone. The trabecular bone loss is three times more than
the accelerated bone loss. There is decreased secretion of parathyroid hormone and increased
secretion of calcitonin. There is also functional impairment in 25-Vitamin D hydroxylase activity
with decreases in production of 1,25(OH)(sub 2) D and therefore decreases in calcium absorption.
Any defect in calcium absorption may aggravate bone loss. Fractures in type I osteoporosis occur
most frequently in vertebrae, distal aspect of radius and intertrochanteric region of the femur. The
spine in type I osteoporosis shows loss of structural trabeculae, and weakened vertebrae and may
predispose to acute collapse. The vertebral bodies are prone for fracture in osteoporosis. The
vertebral fractures are usually of the “crush” type associated with large deformation and pain. The
main reason for fractures of the vertebral body and distal radius is due to the fact that they contain
large amounts of trabecular bone. The other most common fracture of the radius is the Colles’
fracture. Since there is great concern about the development of breast and endometrial hyperplasia,
the treatment for all patients with type I osteoporosis is supplementation with calcium preparations.
Type II (“Senile”) osteoporosis is caused due to long-term calcium deficiency. There is an age
related decline in renal production of 1,25 Vitamin D with subsequent hyperparathyroidism and
bone loss, which affects patients over the age of 75. There is an equal loss of cortical and trabecular
bone with low bone turnover. In type II osteoporosis, fractures occur most often in vertebrae and the
femoral neck, followed by fractures of pelvis, humerus and tibia.

In this clinical study, low calcium and increased phosphorus probably due to hypocalcemia were
observed before treatment. After 6 months of OST-6 medication, there was a significant increase in
the serum calcium and a considerable drop in serum phosphorus levels. This proves that OST-6
helps in absorption of natural calcium. It was also observed that OST-6 produced increased bone
density within a span of 6 months with reduction in bone loss. There was improvement in the ‘T’
score, which showed that OST-6 could be a useful therapy in patients who have osteopenia or
osteoporosis. There was also improvement in the clinical signs and symptoms of osteoporosis. The
joint swelling, pain and stiffness, which was present in some patients probably due to co-existing
osteoarthritis also improved. This could be due to the presence of a plant resin named Commiphora
wightii, which has both anti-osteoporotic and anti-arthritic properties.

CONCLUSION
This study was conducted for 6 months and there was a statistically significant improvement in all
the patients. However, long-term studies involving 1-2 years of treatment may be required to see the
efficacy in remodeling the bone to its normal architecture. All the biochemical and hematological
parameters were normal indicating the safety of OST-6 in the population of patients studied.

REFERENCES
1. Matkovic V, Jelic T, Wardlaw GM, Ilich JZ, Goel PK, Wright JK, et al. Timing of peak bone
mass in caucasian females and its implication for the prevention of osteoporosis. J Clin Invest
1994; 93: 799-808.
2. Teegarden D, Proulx WR, Martin BR, Zhao J, McCabe GP, Lyle RM, et al. Peak bone mass
in young women. J Bone Miner Res 1995; 10: 711-5.
3. Bonjour J-P, Theintz G, Buchs B, Slosman D, Rizzoli R. Critical years and stages of puberty
for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab
1991; 73: 555-63.
4. Ott SM. Bone density in adolescents. N Engl J Med 1991; 325: 1646-7.
5. Wheeless, C.R., Wheeless Textbook of Orthopaedics (Electronic textbook):
http://www.medmedia.com.
6. Lendsay Nievs. Milk and bone. BMJ 1994; 308: 930-1.
7. Nadkarni KM. Indian Materia Medica. Vol 1, 1996, Popular Prakashan Pvt. Ltd., Bombay,
1198.
8. Nadkarni KM. Indian Materia Medica. Vol. 1, 1996, Popular Prakashan Pvt. Ltd., Bombay,
1292.
9. Nadkarni KM. Indian Materia Medica. Vol. 1, 1996, Popular Prakashan Pvt. Ltd., Bombay,
167.
10. Asundi RK and Dixit RM. Spectrographic and X-ray fluorescence analysis of a class of
Ayurvedic medicines – Calcium Bhasmas. J Res Ind Med Yoga Homeo 1978; 13: 90-5.
11. Mitra SK, Venkataranganna MV, Gopumadhavan S, Mohamed Rafiq, Anturlikar SD,
Venkatesha Udupa, U, et al. The beneficial effect of OST-6 (OsteoCare), a herbomineral
formulation, in experimental osteoporosis. Phytomedicine 2001: 8: 195-201.
12. Consensus development conference: diagnosis, prophylaxis and treatment of osteoporosis. Am
J Med 1993; 94: 646-50.
13. Wasnich RD, Ross PD, Heilbrun LK, Vogel JM. Prediction of postmenopausal fracture risk
with bone mineral measurements. Am J Obstet Gynecol 1985; 153: 745-51.
14. Hui SL, Slemenda CW, Johnston CC. Age and bone mass as predictors of fracture in a
prospective study. J Clin Invest 1988; 81: 1804-9.
15. Gardsell P, Johnell O, Nilsson B. The predictive value of bone loss for fragility fractures in
women: a longitudinal study over 15 years. Calcif Tissue Int 1991; 49: 90-4.
16. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et al. Bone density at
various sites for prediction of hip fractures. Lancet 1993; 341: 72-5.
17. Mazess RB, Barden H, Ettinger M, Schultz E. Bone densitometry of the radius, spine and
proximal femur in osteoporosis. J Bone Miner Res 1988; 3: 13-8.
18. Melton LJ, Atkinson EJ, O'Fallon WM, Wahner HW, Riggs BL. Long-term fracture
prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993; 8:
1227-33.
19. Cummings SR, Kelsey JL, Nevitt MC, O’Dowd KJ. Epidemiology of osteoporosis and
osteoporotic fractures. Epidemiol Rev 1985; 7: 178-208.
20. National Institutes of Health, Office of Medical Applications of Research. Osteoporosis:
Consensus Conference. J Am Med Assoc 1984; 252: 799-802.
21. Gallagher JC, Melton LJ, Riggs BL, Bergstrath E. Epidemiology of fractures of the proximal
femur in Rochester, Minnesota. Clin Orthop 1980; 150: 163-71.
22. Cumming RG. Calcium intake and bone mass: a quantitative review of the evidence. Calcif
Tissue Int 1990; 47: 194-201.
23. Dalen N, Hellstronm LG, Jacobson B. Bone mineral content and mechanical strength of the
femoral neck. Acta Orthop Scand 1974; 47:503-8.
24. Weaver CM. Calcium bioavailability and its relation to osteoporosis. Proc Soc Exp Biol Med
1992; 200: 157-60.
25. Horsman A, Currey JD. Estimation of mechanical properties of the distal radius from bone
mineral content and cortical width. Clin Orthop 1983; 176: 298-304.
26. Norman, AW. Vitamin D. In: Brown ML, editor. Present Knowledge in Nutrition, 6th edition,
1990, International Life Sciences Institute Nutrition Foundation, Washington D.C., 108-16.