Chinese Medical Journal 2002;115(3):402-404
Treatment of osteoporosis in men using dehydroepiandrosterone sulfate

SUN Yiping 孙宜萍,  MAO Minwei 毛敏伟,  SUN Lihua 孙丽华,  FENG Yingying 冯缨缨,  YANG Jianfen 杨建芬,  SHEN Peihua 沈佩华

SUN Yiping 孙宜萍 (Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai 20023 3, China)

MAO Minwei 毛敏伟 (Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai 20023 3, China)

SUN Lihua 孙丽华 (Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai 20023 3, China)

FENG Yingying 冯缨缨 (Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai 20023 3, China)

YANG Jianfen 杨建芬 (Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai 20023 3, China)

SHEN Peihua 沈佩华 (Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai 20023 3, China)

Correspondence to:Sun Yiping,Department of Gerontology, Shanghai Sixth P eople’s Hospital, Shanghai 200233, China (Tel: 021- 64369181 ext 8475. Fax:021- 64753413. E-mail:Yipings@sh163b.sta.net.cn)
Keywords
dehydroepiandrosterone;dehydroepiandrosterone sulfate;osteoporosis
Abstract
Objective To study the effect of dehydroepiandrosterone sulfate (DHEAS) treatment of osteo porosis in men with TBMD≥2.5SD.
Methods Eighty- six patients were randomly divided into two groups: treatment group (n= 44) and control group (n=42). DHEAS (100 mg q.d.) was given to the treatment group for 6 months. Bone mineral density, (BMD), biochemical markers of bone absorption and formation and other serum biochemical markers were measured before and after DHEAS treatment. Drug side effects were also evaluated.

Results
After oral administration of DHEAS (100 mg q.d.) for 6 months, the serum concen trations of DHEAS and IGF- Ⅰ in the treatment group were 93.75%±16.1% and 1 7.71%±4.2% higher respectively than those in the control group (P<0.01) . The BMD of L2, L3, L4, L2- 4 and Neck sections increased in the treatment group by 2.65%±0.65%, 2.70%±0.48%, 3.10%±0.41%, 2.82%±0.37% and 2.32%±0 .31%, respectively, as compared with that the control group (P<0.05 or 0. 01). No significant changes were observed in serum FT, E2 and PSA concentrati ons in the treatment group as compared with the control group.

Conclusion
The treatment of osteoporosis in men with DHEAS is safe and effective.

In the past, the study of primary osteoporosis focused on women, especially on bone loss and osteoporosis related to menopause. Hormone replace ment therapy has become one of the priority solutions to treating osteoporosis i n postmenopausal women. However, from current epidemiological investigations, male osteoporosis is also an important public health problem which threatens th e life quality of aging men. Prevention and cure of male osteoporosis has not b een well studied, so our objective was to explore a way to treat osteoporosis in men.

METHODS

Subjects
Eighty- six presenile and senile male outpatients and inpatients were enrolled f rom O ctober 1997 to June 1999. All patients received both physical and laboratory examinations. Those with diseases affecting bone metabolism such as diabetes, kid ney disease or thyroid diseases were excluded. Diagnosis of primary osteoporosi s was based on the WHO new standard of decrease in measured bone mineral densit y (BMD). Patients were randomly divided into two groups. Forty- four patie nts with an a verage age of 68.28±5.01 years (58-85 years) were in the therapeutic group; 4 2 patients with an average age of 70.38±6.74 years (58-88 years) were in th e control group. There were no significant differences between the two groups i n age, BMD and serum biochemical parameters at pre- treatment ( P >0.05).

Methods
Patients in the treatment group took dehydroepiandrosterone sulfate (DHEAS) 100 mg once a day, calcium salt 150 mg three times a day and Vitamin D3 500 IU o nce a day. Patients in the control group took calcium salt 150 mg three times a day and Vitamin D3 500 IU once a day. The patientswere treated for 6 months during which no agent affecting bone metabolism was taken. The BMD of L1- 4, femoral neck, ward’s triangle, intertrochanter and total was measured using a bi- energy X- ray absorption BMD instrument (HOLOGIO, GDR 2000 ) . Serum calcium, phosphorus and alkaline phosphates were measured by automati c analyser and serum osteocalcin (BGP) and pyridinoline (PYD) by EL ISA. Reagents were from the Metra Biosystems Company. The differences within batches were 4.8%-10.0%, the differences among batches were 4.8%-9.0% respec tively. DHEAS, FT, E 2 , PTH and IGF- Ⅰ were measured with radio- immunoassay . The differences within batches were 6.0%-9.8%, 3.2%-4.3%, 5%, 2.7%-2.9% , 6.6%-9.9% respectively. Meanwhile, the differences among batches were 4.9 %-9.5%, 3.4%-5.5%, 7.9%-8.6%, and 3.9%-11.2% respectively. Kits were sup plied by DEPU Company, Tianjin, DRC Company, USA, Metra Company, USA, and Chiron Company, USA.

Statistics
Results were analyzed by SAS software and presented as mean ±s. The change between pre- treatment and post- treatment (△%)=[pre- treatment-post- t reatment/pre- treatment]×100%. The difference between the two groups was anal yzed with t test.

RESULTS

BMD differences between pre- treatment and post- treatment
There were no significant differences between the therapeutic and control groups in age and BMD at pre- treatment ( P >0.05).BMD of the therapeutic gro up s howed a general increase, except for the femoral intertrochanter and total BMD. BMD of L 2 and, L 3 and L 4 increased by 2.65%±0.62%, 2.70%±0.48%, 3.1%±0.31% respectively, and 2.82%±0.37% on average. BMD of the neck o f the femur increased by 2.32%±0.31%. Compared to the control group, all dif ferences were significant.

Differences in biochemical parameters in serum before and after trea tment
There were no significant differences between the therapeutic and control groups in age and biochemical parameters in serum at pre- treatment ( P >0.05). Ch anges in biochemical parameters in serum before and after DHEAS treatment were c oncentrations of DHEAS and IGF- Ⅰ in the treatment group increased by 93.75%± 16.1% and 17.71%±4.2% respectively as compared with the control group. The difference between the two groups was significant ( P <0.01). The concentrat ion of PYD in urine decreased by 0.65%±6.1% in the treatment group as compare d with the values before treatment, and increased by 32.95%±7.1% in the contr ol group, a significant difference ( P <0.05). No difference was observed i n free testosterone, E 2 and PSA between the groups.

DISCUSSION

Osteoporosis in men is the result of multiple factors related to age and belon gs to type Ⅱ osteoporosis, in most cases. Several studies show that the reduct ion in bone mineral density is related to age and the rate of reduction in aging men is similar to that in aging women.[1,2]The imbalance between bone a bsorption and bone formation leads to reduction in bone mineral density because the rate of bone absorption exceeds the rate of bone formation. Strong evidence shows that the reduction in bone mineral density in aging women was due to the lack of estrogen after menopause, resulting in an increase in bone absorption an d decrease in bone formation. However, insufficient evidence was available for aging men. Some researchers found that the concentration of bone formation mark er BGP declined gradually with increasing age while the amount of biomarker of b one absorption showed no change.[3- 5]From this study, the marker of bon e absorption, PYD, declined significantly after oral administration of DHEAS, pr oviding evidence that oral administration of DHEAS can inhibit bone absorption a nd impede the d evelopment of osteoporosis. Elevation of PTH and reduction in bone mineral den sity can be observed in healthy aged people. PTH levels in the treatment group decreased significantly after the administration of DHEAS, indicating that admi nistration of DHEAS may inhibit the secretion of PTH and decrease bone absorptio n. Many studies show that the concentration of serum androgen in patients suffe ring from hip fractures were much lower than the concentrations in control group of similar age and no fracture.[5,6]Lack of androgen may be a direct cau se of red uced bone formation and a reduction of bone mineral density in aging men. Ani mal studies show that testosterone can stimulate bone formation.[7]Testostero ne m ay be converted to di- hydro- testosterone through target cells or converted to estrogen by aromatase, which may maintain the quantity of bone mineral. As a pr ogenitor of estrogen, DHEAS has multiple physiological and pathological effects . Levels of DHEAS decrease with age in humans. Elevation of BMD in the treatme nt group after the administration of DHEAS observed in this clinical study may b e the effect of di- hydro- testosterone or estrogen originating from DHEAS.[ 8,9] Furthermore, there is no change in free testosterone, PSA or estradiol a fter treatment, indicating that the administration of DHEAS may have no adverse effects on the prostate. (Table.1) (Table.2)

Many have shown that a decrease in growth hormone secretion and changes in IGF- Ⅰ may lead to bone aging and a reduction in bone density with aging. IGF- Ⅰ can stimulate mitosis of cells involved in bone metabolism and/or initiate th e activity and differentiation of these cells, especially up- regulating the qua ntity and function of osteoblasts. At the same time, IG F- Ⅰ can inhibit the transcription of collagenase in matrix, decrease the degradation of bone collagen and stimulate the recovery of osteoclasts to regulate bone absorption. The conc entration of IGF- Ⅰ positively correlates with BMD. Administration of DHEAS ca n elevate levels of IGF- Ⅰ, indicating that the administration of DHEAS may inc rease BMD through stimulating the secretion of IGF- Ⅰ.

Administration of DHEAS can be a safe and effective treatment for osteoporosis i n aging men and the mechanism of action should be studied further. Its conclu sive role demands further clinical observation with a larger clinical sample.

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  1. Shanghai Science Committee,No. 964119024;