text: suitable serm compounds for use in the present invention are triphenylalkene or triphenylalkane compounds such as compounds disclosed in wo 01 / 36360 , u . s . pat . no . 4 , 996 , 225 , u . s . pat . no . 4 , 696 , 949 , u . s . pat . no . 5 , 750 , 576 , wo 99 / 42427 and the toremifene metabolites disclosed in l . kangas , cancer chemother pharmacol ( 1990 ) 27 : 8 - 12 . as examples of specific drugs disclosed in the aforementioned references can be mentioned toremifene and ospemifene . tamoxifen and its derivatives such as 4 - hydroxytamoxifen , alpha - hydroxytamoxifen , n - desmethyltamoxifen , n , n - didesmethyltamoxifen , deaminotamoxifen , and droloxifene and iodoxifene also examples of suitable serms of triphenylalkene structure . according to preferred embodiment , the therapeutically active compound is a serm of triphenylalkene structure . especially a compound of formula ( i ) or a geometric isomer , a stereoisomer , a pharmaceutically acceptable salt , an ester thereof or a metabolite thereof is preferred : the method of preventing or treating osteoporosis with ospemifene and related compounds according to this invention in individuals with increased bone turnover is particularly useful when treating women during or after the menopause . however , the method according to this invention is not restricted to women in this age group . the term “ metabolite ” shall be understood to cover any ospemifene or ( deaminohydroxy ) toremifene metabolite already discovered or to be discovered . as examples of such metabolites can be mentioned the oxidation metabolites mentioned in kangas ( 1990 ) on page 9 ( tore vi , tore vii , tore xviii , tore viii , tore xiii ), especially tore vi and tore xviii , and other metabolites of the compound . the most important metabolite of ospemifene is 4 - hydroxyospemifene , which has the formula the use of mixtures of isomers of compound ( i ) shall also be included in this invention . the wording “ increased bone turnover ” means that both bone resorption and formation of new bone are increased . as a normal value for bone resorption in postmenopausal women is considered a bone resorption of at least 65 nmol / mmol crea , using amino terminal telopeptide of type i collagen measured in urine ( u - ntx ) as marker or at least 680 microgram / mmol crea , using carboxy terminal telopeptide of type i collagen measured in urine ( u - ctx ) as marker . as a normal value for bone formation in the same group is considered a bone formation of at least 170 microgram / i , using carboxy terminal propeptide of type i procollagen measured in serum ( s - picp ) as marker , or at least 84 microgram / i , using amino terminal propeptide of type i procollagen measured in serum ( s - pinp ) as marker . a particular good response to the administering of ospemifene is observed in individuals with at least 5 %, preferably at least 10 % increased bone turnover , measured as well as bone resorption as bone formation . an especially important population benefiting from the method according to this invention is postmenopausal women having a bone resorption , measured as u - ntx , which is at least 70 nmol / mmol crea , preferably at least 80 nmol / mmol , and a bone formation , measured as s - picp , being at least 180 microgram / i . particularly suitable markers for measuring bone resorption are crosslaps measured from serum and trap5b , also measured from serum . crosslaps is marker reporting the activity of osteoclasts and trap5b is a marker revealing the number of the osteoclasts . the value indicating a level of normal bone turnover for both of these markers is about 3 . increased bone resorption is often registered as value 6 , i . e . an increase of 100 %. these markers are thus very sensitive to changes in bone resorption . according to a particularly preferred alternative , the bone resorption is measured using as markers a combination of crosslaps and trap5b , both measured from serum . according to previous data , the optimal clinical dose of ospemifene is expected to be higher than 25 mg daily and lower than 100 mg daily . a particularly preferable daily dose has been suggested in the range 30 to 90 mg . at the higher doses ( 100 and 200 mg daily ), ospemifene shows properties more similar to those of tamoxifen and toremifene . the invention will be disclosed more in detail in the following non - restrictive experimental section . in female rats high bone turnover can be induced by ovariectomy ( ovx ). rapidly , within days after ovx the number of osteoclasts increases and resorption markers increase . shortly after ovx the bone formation is also increased , but due to the absence of bone protecting estrogens , the balance is towards bone loss . the bone loss , however , reaches within a few months a new balance , where the bone mass is lower than at baseline , but the rates of formation and resorption are equal . estrogens can prevent the bone loss effectively , when it is administered immediately after ovx . if the administration is started months later , the bone structure has been changed and estrogens do not have as strong beneficial effect . high bone turnover was induced to 2 - 4 months old female rats by ovariectomy ( ovx ). treatment with ospemifene was started at different time points after ovx : 1 day , 1 , 2 , and 3 months after ovx . bone resorption was evaluated in short - term by bone specific trap5b , which is a protease secreted specifically by osteoclasts , and later by pyridinoline / deoxypyridinoline cross links , which are degradation products of bone collagen and excreted in the urine . finally , during autopsy , usually after 3 months treatment , trabecular bone mineral density was measured . female rats , 2 months old , n = 6 in each group , were ovariectomized . during ovx a blood sample was taken to measure the base line value for trap5b . trapb - values were measured also after 2 days . the working hypothesis was that ovx increases trap5b concentrations at 2 days , because osteoclast number rapidly increases . on the other hand ospemifene was expected to lower the osteoclast number and thus decrease the trap5b at 2 days . as shown in table 1 , this was the case . the beneficial effect of ospemifene at the time of high bone turnover is thus obvious . female rats , age about 4 months , were ovariectomized . treatment with vehicle or ospemifene was started at different periods after ovx ( from one day to 3 months ). the ospemifene doses were 5 , 10 or 25 mg / kg and the treatment period was 3 months . evaluation of the bone occurred by bone mineral density measurement of tibial trabecular bone after the treatment and in some groups also by bone collagen degradation products excreted in the urine . table 3 effect of ospemifene on bone degradation markers 30 days after ovx . the administration of ospemifene was started one day after ovx and continued daily until measurements . urine total pyridinoline / deoxypyridoline crosslinks were measured in the urine . sham means rats , which were operated like ovx animals , but the ovaries were not removed . ovx + ospemifene ovx sham 5 mg / kg 25 mg / kg change from base line 165 ± 42 3 ± 22 55 ± 16 33 ± 20 at 30 days a strong increase in crosslinks during the first month after ovx ( during high bone turnover ) is evident . ospemifene significantly decreases the excretion of crosslinks , which is a resorption marker . in the clinical trials , bone turnover was evaluated by measuring the levels of bone formation markers in serum and bone resorption markers in urine . both bone resorption markers e . g . amino terminal telopeptide of type i collagen ( u - ntx ) and carboxy terminal telopeptide of type i collagen ( u - ctx ) and formation markers e . g . amino terminal propeptide of type i procollagen ( s - pinp ) and carboxy terminal propeptide of type i procollagen ( s - picp ) are increased in menopause , indicating high bone turnover . bone antiresorptive therapy decreases these values reflecting inhibition of bone turnover . in the two 12 - week phase ii studies , 209 postmenopausal women were treated with 30 mg , 60 mg or 90 mg ospemifene per day . most of the women had normal bone marker levels at baseline . in those who had high bone marker levels at baseline a large decrease both in formation and resorption bone markers was seen with daily doses 60 mg and 90 mg . as examples , individual changes in u - ntx and s - picp are shown in fig1 and 2 . in fig3 and 4 , changes at 12 weeks relative to baseline in the bone markers were plotted versus the corresponding baseline values in the placebo - controlled phase ii study . large baseline values resulted in large reductions in the primary endpoints . this tendency was obvious for the formation markers s - pinp and s - picp as well as for the resorption markers u - ctx and u - ntx in subjects treated with 60 mg or 90 mg daily doses . the upper limit of normal range in women was 84 μg / l for s - pinp , 65 nmol / mmol crea for u - ntx , 170 μg / l for s - picp and 680 μg / mmol crea for u - ctx . in women with the highest bone marker levels at baseline the decrease was most dramatic . the clinical tests show that administration of ospemifene is useful in decreasing bone turnover in individuals with increased bone turnover . it is known that other drugs , such as bisphosphonates very effectively reduce bone resorption as a result of inactivation of osteoclasts . however , such a complete inactivation of osteoclasts has an adverse effect on the formation of new bone , because osteoclasts are important to eliminate old bone so that new bone can be created . therefore , prolonged bisphosphonate treatment tends to result in a very brittle bone structure . ospemifene has a gentle effect on the osteoclasts in that it decreases the number of the cells but it does not cause complete inactivation of the same . therefore , ospemifene decreases the bone resorption to a certain extent , but it allows the osteoclasts to work and therefore new bone to be formed . the result is a balanced decrease in bone resorption which does not adversely affect the bone formation . it will be appreciated that the methods of the present invention can be incorporated in the form of a variety of embodiments , only a few of which are disclosed herein . it will be apparent for the expert skilled in the field that other embodiments exist and do not depart from the spirit of the invention . thus , the described embodiments are illustrative and should not be construed as restrictive . kangas l . biochemical and pharmacological effects of toremifene metabolites . cancer chemother pharmacol 27 : 8 - 12 , 1990 . kauffinan r f , bryant h u . selective estrogen receptor modulators . drug news perspect 8 : 531 - 539 , 1995 .