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Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update
Bisphosphonates are potent inhibitors of bone resorption and considered as a gold standard and are generally recommended as first-line therapy in patients with osteoporosis. Though bisphosphonates are shown to significantly reduce the risk of vertebral, non-vertebral and hip fractures, recent reports suggest a possible correlation between long-term bisphosphonate therapy and the occurrence of insufficiency fractures owing to prolonged bone turnover suppression. We report a patient with non-traumatic stress fractures of bilateral femoral shafts related to long-term bisphosphonate therapy indicating the need for a critical evaluation of patients with long-term bisphosphonate therapy.
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Transient osteoporosis of the hip (TOH) is a rare disorder of unknown etiology that is characterized by acute onset of disabling bone pain. The locally increased bone turnover and low bone mineral density (BMD) associated with this disorder indicate a potential role for an antiresorptive agent such as bisphosphonate as a treatment. A previously healthy 46-year-old man developed the sudden onset of pain in his right buttock and inguinal area, especially during walking and caused him to limp. A thorough medical workup including X-ray, MRI, and bone SPECT revealed transient osteoporosis of the hip, and he was treated with an infusion of zoledronate (5 mg). Two weeks later, he was fully recovered from pain and the gait disturbance. A follow-up MRI of the hip joint taken after 6 months showed complete resolution. The use of intravenous zoledronate provided a successful outcome in the treatment of TOH. The possibility of TOH should be considered in patients complaining of sudden hip pain and a limping gait. MR imaging played an important role for differentiation of TOH from other aggressive conditions with long term sequelae.
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Method: The subjects were 21 hemiplegic stroke patients, 11 men, 10 women, age 60.3⁑8.4 years and 21 age and sex matched controls. We measured BMDs in patients, and compared BMDs of the affected and unaffected sides, and compared BMDs of each affected and unaffected sides with controls, and evaluate the relationship between BMDs with functional parameters.
Results: Stroke patients have high prevalence of osteoporosis and osteopenia, and affected side BMDs of patients were lower in upper and lower limbs compared with the controls. BMDs of the affected side were lower for the upper and lower limbs compared with the unaffected side.
Conclusion: Stroke patients have high prevalence of osteoporosis. Therefore early rehabilitative care, including weight- bearing and outdoor ambulation, is essential for hemiplegic stroke patients in order to prevent possible complications, especially osteoporotic fractures. (J Korean Acad Rehab Med 2003; 27: 13-20)
Objective: To examine the relation of shoulder adhesive capsulitis and local bone loss to affected limb.
Method: Twenty-nine patients with the adhesive capsulitis of the shoulder were studied. For reference, 29 patients, without history of injury or disease in the upper limbs, were randomly selected. Areal bone mineral density (BMD) was measured from the proximal humerus, distal humerus and forearm of upper limbs using a ProdigyⰒ (Lunar, USA). The BMD of the affected side versus the unaffected were compared.
Results: The reference group: no significant difference between the mean BMDs in the right and left upper limb. The adhesive capsulitis group: 1) The mean BMD in the proxi-mal humerus of the affected upper limb was significantly lower than the unaffected limb (0.85 g/cm2 vs 0.88 g/cm2; p＜0.05). 2) No significant difference between the mean BMDs in the distal humerus of the affected and unaffected limb (1.10 g/cm2 vs 1.10 g/cm2). 3) No significant difference between the mean BMDs in the forearm of the affected and unaffected limb (0.82 g/cm2 vs 0.82 g/cm2).
Conclusion: In patients with adhesive capsulitis of the shoulder, the mean BMD of the affected limb, compared with the unaffected side, was significantly lower in the proximal humerus. But distal humerus and forearm showed no significant side-to-side differences. (J Korean Acad Rehab Med 2002; 26: 327-331)
Objective: To investigate the changes of bone mineral density (BMD), biochemical bone markers, and lipid profiles after combination therapy of continuous hormonal replacement therapy (c-HRT) and alendronate in postmenopausal osteoporosis.
Method: We studied 89 women with postmenopausal osteoporosis (T-score＜2.5) who visited at Department of Rehabilitation Medicine, Kosin Medical Center from August 1999 to March 2001. Subjects were divided into two groups; Group I (n=40), treated with estrogen and alendronate (10 mg/day), and Group II (n=49), treated with estrogen alone. BMD at the lumbar spine and femur, osteocalcin, urine deoxypyridinoline and lipid profiles were measured at baseline and 1-year after treatment.
Results: 1) BMD at the lumbar spine increased significantly
in two groups, and BMD in Group I increased significantly more than that in Group II. But, change of BMD on femoral neck was not significantly different. 2) Biochemical bone markers (osteocalcin and urine deoxypyridinoline) decreased significantly in two groups. 3) Total cholesterol and LDL cholesterol decreased significantly in two groups, but HDL cholesterol and triglyceride showed no significant change in two groups. There was no significant differences between two groups in lipid profiles.
Conclusion: We concluded that combination therapy with c- HRT and alendronate in postmenopausal osteoporosis was more effective than c-HRT, which would not influence on positive effect of estrogen for lipid metabolism. (J Korean Acad Rehab Med 2002; 26: 208-214)
Objective: To investigate the changes of bone mineral density (BMD), biochemical bone markers, and lipid profiles according to the duration of menopause in postmenopausal osteoporosis patient receiving continuous hormonal replacement therapy (c-HRT).
Method: Sixty seven patients with postmenopausal osteoporosis who have been under c-HRT for more than two years were used as subjects and divided into two groups according to the time past menopause: group I (0∼10 years), group II (over 10 years). The changes of BMD, biochemical bone markers, lipid profiles on one year and two years of c-HRT were comparatively analyzed in each group.
Results: 1) BMD of lumbar vertebra was increased and biochemical bone markers were decreased after c-HRT in both groups, but BMD of femur from both groups showed no statistical significant changes. 2) The changes in lumbar vertebra, deoxypyridinoline and osteocalcin were significantly higher after first one year than next one year of c-HRT in both groups, with no statistical differences between two groups. 3) Total cholesterol and LDL-cholesterol were decreased, but HDL-cholesterol and triglyceride showed no significant changes after c-HRT in both groups.
Conclusion: The effects of c-HRT on BMD, biochemical bone markers, lipid profiles were not influenced by postmenopausal period. And the effects of c-HRT during first one year were more prominent than those of c-HRT during next one year.
Objective: The purpose of this study is to evaluate the loss of bone mineral density on ovariectomized (ovx) rat in young and old rats.
Method: Total 110 Sprague-Dawley female rats which composed of 3 months aged 88 rats and 12 months aged 22 rats were used. They were divided randomly into 5 ovx groups (15 rats for each group) and 5 sham operation group (7 rats for each group). The bone mineral density was measured by Hologic 4,500 Fan Beam bone densitometry at the time of second postoperation week, 4th week, 8th week, and 16th week in young aged group and 4th, 8th week in old aged group.
Results: The bone mineral density in young ovx rats was decreased measured at 2 week, 4 week and 8 week, but not 16 week compared with that of sham operation rats (p＜0.05). In old rats, there was no significant change in bone mineral density between ovx and sham group (p＞0.05).
Conclusion: For the purpose of osteoporosis inducing experiment, young aged rat is more reliable for the detection of bone density change than old aged rat and the bone mineral density change will be continued at least 16 week postovariectomy period.
Objective: To evaluate the efficacy of growth hormone in reversing glucocorticoid-induced musculoskeletal changes including osteoporosis and myopathy in rats.
Method: Experimental rats were divided into five groups and each group was composed of 10 rats. The group 1 was administered with saline, group 2 with growth hormone, group 3 with glucocorticoid, group 4 with combined dosages of growth hormone and glucocorticoid, and group 5 with glucocorticoid for 4 weeks and then growth hormone for another 4 weeks. All injections were carried out every other day for 8 weeks. The half of animals were sacrificed after 4 weeks and another half after 8 weeks in each group. The triceps surae muscle was biopsied and examined histologically for the evaluation of mean area of muscle fiber. The femur was removed and dissected for the measurement of its weight, length, and diameter. The bone mineral density of the femur was measured by a dual energy X-ray absorptiometer.
Results: Administration of growth hormone partially reversed the complications of steroid such as decrease in body weight, decrease in weight, length, diameter, and bone mineral density of femur, and decrease in mean area of muscle fiber.
Conclusion: This study indicated that growth hormone could be applied for the management of steroid-induced osteoporosis and myopathy.
Objective: To examine the correlation between bone mineral density and intervertebral disc degeneration through retrospective study.
Method: Bone mineral density (BMD) and Magnetic resonance (MR) image of lumbar spine from 61 postmenopausal women were assessed to examine the correlation between bone mineral density and intervertebral disc degeneration. We determined BMD of lumbar spine using the dual energy X-ray absorptiometry (DEXA). And we evaluated signal intensity of intervertebral disc, disc height and disc herniation at each lumbar disc level using the MR image. The correlation between BMD (mean value of 2nd, 3rd and 4th lumbar spine BMD) and the sum of grading scores of intervertebral disc degeneration was assessed in all the patients.
Results: There was a positive correlation between BMD of lumbar spine and the sum of grading scores of intervertebral disc degeneration (r=0.415, p value=0.00087).
Conclusion: Bone mineral density has an inverse correlation to intervertebral disc degeneration and which is important when considering degenerative spinal disease and osteoporosis.
Objective: To determine whether estradiol (E2), lipid profile, biochemical markers, and bone mineral density (BMD) are related according to postmenopausal period.
Method: One hundred fifty four women were divided into four groups according to the time past menopause: group I (0∼5 years), group II (6∼10 years), group III (11∼15 years), group IV (more than 16 years). Group I, II, III were subdivided into osteoporosis group (t-score＜2.5) and non-osteoporosis group (t-score≥2.5). E2, lipid profile, osteocalcin, alkaline phosphatase, deoxypyridinoline, and BMD by DEXA were measured in all groups.
Results: There were significant inverse correlation between BMD and postmenopausal period (p＜0.05). Deoxypyridinoline and osteocalcin were correlated with postmenopausal period but there was no statistical significance. Deoxypyridinoline and osteocalcin were increased in osteoporosis group compared to non-osteoporosis group but there was no statistical significance. E2 had significant inverse correlations with postmenopausal period (p＜0.05). E2 had no correlation with factors such as biochemical markers and lipid profile in group I, II, III but had adverse correlation with deoxypyridinoline in group IV.
Conclusion: No specific biochemical markers regarding the duration of menopause were found. Regardless of the duration of menopause, checking both osteocalcin and deoxypyridinoline was statistically significant for the evaluation of postmenopausal osteoporosis.
Objective: The purpose of this study was to evaluate the severity and frequency of osteoporosis of the foot in patients with diabetes mellitus using bone densitometry, and to determine whether plain radiologic evaluation can be used as a cheap and reliable screening of osteoporosis.
Method: We studied plain X-ray including AP and lateral views of the feet of the patients. Bone densitometry studies were performed on the feet of both diabetic and age-matched control groups.
Results: Forefoot bone densitometry scores were significantly lower in the male diabetic group compared to the control group (p＜0.05). Furthermore, the female diabetics had significantly lower bone densitometry scores for forefoot and hindfoot than the control group (p＜0.05). Bone densitometric evaluation of the diabetic patients' feet revealed scores significantly lower than those of the controls in cases which the radiologist interpreted as normal finding in plain roentgenogram alone (p＜0.05).
Conclusion: Plain radiologic studies of the feet in patients with diabetes mellitus are not effective in identifying osteoporotic change; thus, they should not be used as the screening method of diabetic foot lesions.
Objective: This study was designed to evaluate the effect of growth hormone on bone mineral density of corticosteoid-induced osteoporosis in male rat.
Method: Twenty Sprague-Dwaley male rats was studied, divided into four group, each group has 5 rats. The group 1 was treated with saline. The group 2 was treated with corticosteroid (Methylprednisolone 10 mg/kg). The group 3 was treated with corticosteroid and growth hormone (recombinant human growth hormone 0.5 IU/kg). The group 4 was treated with growth hormone after corticosteroid treatment. The treatment duration was 6 weeks for each group. After six weeks of hormone administration, the animals were sacrificed, the bilateral femur were removed and tested for bone mineral density using dual energy X-ray absorptiometry and examined histomorphometrically.
Results: Administration of growth hormone after corticosteroid therapy, the growth hormone could reverse the decrease in body weight and bone mineral density induced by corticosteroid therapy (p＜0.05).
Conclusion: When growth hormone is administrated after corticosteroid therapy, the growth hormone can protect the osteoporosis in male rats induced by a high dose of corticosteroid.
Objective: To determine the correlation between osteoporosis and the related factors through retrospective study.
Method: Data from 1002 patients (834 women and 168 men) were analyzed through medical records [bone mineral density (BMD), age, height (Ht), body weight (BW), body mass index (BMI), and the accompanying conditions]. BMD of lumbar spine (L1-4) and femur (neck, Ward's triangle, trochanter, and shaft) were measured using dual energy x-ray absorptiometry (DEXA) and were correlated with age, Ht, BW, BMI, and accompanying diseases, and fracture incidence.
Results: 1) BMD of lumbar spine and femur neck in women significantly correlated with age and that of lumbar spine in men significantly correlated with BMI, Ht, BW. 2) The accompanying conditions in osteoporosis were diabetes mellitus (5.9%), Cushing syndrome (3.7%), oophorectomy (2.8%), hyperthyroidism (2.6%), and chronic renal failure (1.0%). 3) Fracture sites and their incidences were single spine (4.89%), multiple spine (2.99%), and femur (2.0%). 4) Mean BMD and T-score in fracture group was 0.687±0.16 g/cm2, 3.51±1.3 in lumbar spine and 0.578±0.14 g/cm2, 2.70±1.1 in femur, respectively.
Conclusion: Osteoporosis is a major public health problem among the elderly, demanding effective strategic approach for prevention and treatment. We concluded that further studies of male osteoporosis are required.
Objective: The purpose of this study was to investigate a correlation between the muscle strength of trunk and bone mineral density (BMD) in women.
Method: A total of 218 healthy women participated in the study. Their age ranged from 26 to 72 years. Dual X-ray absorptiometry was used to measure the BMD of lumbar spine and the trunk muscle strength was assessed by a Cybex NORMTM system. Under the standard criteria of World Health Organization for the dual X-ray absorptiometry analysis, we divided spine T-score into three groups(group 1: osteoporosis, group 2: osteopenia, and group 3: normal).
Results: The data revealed a siginificant correlation (r=0.455, p=0.0001) between the age and BMD of lumbar spine. Trunk extensor muscle strength revealed 56.27⁑18.08 Nm (mean⁑SD) in osteoporosis group, 72.84⁑21.69 Nm in osteopenic group, and 77.90⁑22.28 Nm in normal group. Trunk flexor muscle strength was 82.73⁑23.30 Nm in osteoporosis group, 86.00⁑19.77 Nm in osteopenic group, and 98.91⁑18.29 Nm in normal group.
Conclusion: These results indicated that the trunk extensor muscle was weaker than the flexor muscle in osteoporotic group. As the bone mineral density reduced, the strength of both trunk extensor and flexor decreased. However the weakness of trunk flexor occurred at the earlier stage of osteoporosis than the weakness of trunk extensor.
Objective: To evaluate and correlate three biochemical markers of bone turnover and bone mineral density in the lumbar spine.
Method: Eighty seven adults with the low back pain(45 men and 42 women) were enrolled in this study. Bone mineral density in the lumbar spine was evaluated by a quantitative computed tomography. Serum osteocalcin, serum alkaline phosphatase, and urinary deoxypyridinoline were measured in the early morning.
Results: The mean serum osteocalcin values were 5.61 ng/ml in men and 5.68 ng/ml in women. The mean urinary deoxypyridinoline values were 6.54 nM/mM.Cr. in men and 10.0 nM/mM.Cr. in women. Among women, the values of serum osteocalcin and alkaline phosphatase were significantly higher in the postmenopausal group than the premenopausal group(p＜0.01). And, they were inversely related to bone mineral density in lumbar spine.
Conclusion: These findings suggest that the measurement of serum osteocalcin, alkaline phosphatase, and urinary deoxypyridinoline can be used as indirect indicators of the current bone status, and can be effectively used in the evaluation and treatment of osteoporosis.
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