Exhibit 10.12D

NOTE: CONFIDENTIAL TREATMENT REQUESTED. EXHIBIT OMITS INFORMATION THAT HAS
      BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.


                                SECOND AMENDMENT
                                       TO
                OSTEOMARK-registered trademark- LICENSE AGREEMENT


         This  Second  Amendment  to  Osteomark-registered   trademark-  License
Agreement (this "Second Amendment") is effective as of December 24, 1997, by and
between Ostex International, Inc. ("Ostex") and Mochida Pharmaceutical Co., Ltd.
("Mochida").

                                    RECITALS

         A. WHEREAS, Ostex and Mochida are parties to that certain Osteomark-TM-
License  Agreement,  as  amended,  dated as of August  21,  1992  (the  "License
Agreement"),   pursuant  to  which  Ostex   granted  a  license  to  Mochida  to
commercialize the urine-based assay to measure bone resorption in Japan.

         B.       WHEREAS, Section 5.2 of the License Agreement established 
"a flexible pricing formula to enable both Ostex and Mochida to remain 
profitable while selling Finished Product in the Territory."

         C. WHEREAS,  circumstances have changed since the License Agreement was
entered  into  in  1992,  to  such  extent  that:   first,   Mochida's  cost  of
manufacturing  Osteomark  microtiter kits is now  established,  and such cost is
significantly  higher  than  was  anticipated  in  1992;  second,  the  Japanese
government  control  of the  national  health  care  system has  shifted  toward
deregulation, thereby disrupting the reimbursement pricing system upon which the
original  pricing  formula  was  based;  and  third,   Mochida  requires  stable
circumstances  during the initial stage of the Osteomark product launch to avoid
cost, supply, packaging and quality control problems.

         NOW, THEREFORE,  for good and valuable  consideration,  the receipt and
sufficiency of which are hereby acknowledged, the parties agree that the License
Agreement is amended as follows:

                                    AGREEMENT

         1.       Exchange Rate.  Section 4.8 of the License Agreement is 
hereby amended to read in its entirety as follows:

                  4.8 Exchange  Rate.  All monies due Ostex under this Agreement
                      shall be paid in United States Dollars.  The parties agree
                      that the prices stated in Yen in this  Agreement are based
                      on an exchange rate of  (Y)115:$1.  The parties agree that
                      they will share  equally the risk of  fluctuations  in the
                      exchange  rate.  To this end,  the  prices  stated in this
                      Agreement  will be paid in United  States  Dollars  at the
                      exchange rate  determined in accordance with the following
                      formula:

                                            AER  =  115  +  (ER - 115)
                                                             --------
                                                                2

                      where:

                      AER  =  the Agreed Exchange Rate for converting the 
                               stated prices to United States Dollars; and
                      ER   =  the  Exchange  Rate  quoted by the Wall  Street
                               Journal on the date on which Ostex  prepares  the
                               first  draft  of the  relevant  invoice  for each
                               shipment (a copy of the relevant page of the Wall
                               Street  Journal shall be sent to Mochida with the
                               invoice).


<PAGE>

                      Notwithstanding the foregoing,  the transfer price for the
                      shipment of Critical  Reagents  to Mochida  under  Mochida
                      Order No.  MS-970027  shall be  converted  and paid at the
                      spot  exchange  rate quoted by the Wall Street  Journal on
                      December 3, 1997.

         2.       Manufacture and Pricing of Kit Components.  Section 5 of 
the License Agreement is hereby replaced in its entirety by the following 
new Section 5:

                  5.       Supply of Critical Reagents and Kit Components.

                           5.1 Supply of Critical Reagents.  Ostex shall provide
         to  Mochida a supply of the  Critical  Reagents  to be  assembled  into
         Finished Products and to be marketed, promoted, sold and distributed by
         Mochida in accordance with the terms of this Agreement and the relevant
         quality criteria jointly established by Ostex and Mochida (the "Quality
         Criteria").  Such Critical  Reagents shall be manufactured by Ostex, or
         by  one  or  more   third-party   licensees   of   Ostex   at   Ostex's
         responsibility, and shall meet the Quality Criteria.

                           5.2 Manufacture and Supply of Kit Components. Mochida
         shall transfer the right and  responsibility for the manufacture of all
         components of Finished  Products,  other than Finished Product labeling
         and packaging materials, (the "Kit Components") to Ostex by the time to
         be agreed upon between the parties but no later than December 31, 2000,
         on the  terms  and  conditions  set  forth  below.  Mochida  will  file
         applications  with and pursue the approval of the  applicable  Japanese
         governmental  authorities  to obtain  registrations  to import  all Kit
         Components by such date.  Such Kit Components  shall be manufactured by
         Ostex, or by one or more third-party licensees of Ostex, and shall meet
         the Quality  Criteria to be agreed  between  the parties  covering  Kit
         Components.  If or  when  Mochida  requests  Ostex  to  label  the  Kit
         Components, Ostex shall accept such request by Mochida at no additional
         cost,  fee or expense in the following  way: Ostex shall supply Mochida
         with  specifications for the preparation of labels which can be applied
         using Ostex  machinery,  and Mochida  shall supply Ostex with labels in
         Japanese  to be  applied  to such Kit  Components.  In the  event  that
         Mochida finds it difficult to obtain blank label stock meeting  Ostex's
         specifications,  then at Mochida's  option,  Ostex  through its vendor,
         will  supply such stock to  Mochida,  or will print such  labels  using
         Mochida's artwork, at Mochida's cost.

                           5.3      Quantity of Critical Reagents and Kit 
                                    Components.

                                    (a)     Mochida shall provide to Ostex 
         at least sixty (60) days
         prior  to the  commencement  of  each  calendar  quarter,  a  quarterly
         forecast of commercial demand for Critical Reagents (or, if applicable,
         Kit  Components)  to be imported by Mochida into the  Territory  during
         such  quarter.  Mochida shall deliver to Ostex at least sixty (60) days
         prior to the expected  shipment  date a purchase  order for a specified
         quantity of Critical Reagents (or, if applicable, Kit Components).

                                    (b)     Ostex shall deliver to Mochida 
         shipments of Critical
         Reagents or Kit Components (once  responsibility for manufacturing such
         Kit Components has been transferred to Ostex) in quantities  reasonably
         necessary to satisfy the commercial demand for Finished Products within
         the Territory.  Ostex and Mochida shall, from time to time as necessary
         following the  commencement  of commercial  sales,  adjust the terms of
         quantity and  delivery to  correspond  to such  commercial  demand,  in
         accordance with the quarterly forecasts provided by Mochida pursuant to
         Section 5.3(a) above.


<PAGE>

                     NOTE: CONFIDENTIAL TREATMENT REQUESTED

                                    (c)     Notwithstanding the foregoing or 
         any other provision of
         this Agreement, it is understood between Ostex and Mochida that, in the
         event  formats  other  than  the  current  microtiter  format  for  the
         technology  are developed or utilized by the parties,  and the delivery
         of Critical  Reagents or Kit Components for such format pursuant to the
         transfer prices set forth in this Agreement would be less profitable to
         Ostex,  the  parties  agree that they will  renegotiate  such  transfer
         prices in good faith. In any event,  Ostex shall be under no obligation
         to supply  Critical  Reagents or Kit Components to Mochida for a format
         other  than the  current  microtiter  format  at a price  which is less
         profitable than the current pricing for the microtiter format.

                           5.4 Price for Critical  Reagents and Kit  Components.
         Mochida  shall  pay for  each  shipment  of  Critical  Reagents  or Kit
         Components,  within  sixty  (60) days of the date of  invoice  for such
         shipment, the amounts set forth below:

                                    (a)     For all Critical Reagents ordered
         by Mochida prior to
         July 6, 1999 (including  Mochida's Order No. MS-970027),  Mochida shall
         purchase  Critical  Reagents at a price of (Y)XXXXXXXX per kit, payable
         in United States Dollars at the exchange rate set forth in Section 4.8.
         For orders  received  by Ostex on or after July 6, 1999,  Mochida  will
         purchase  quantities of Critical  Reagents at a price of (Y)XXXXXXX per
         kit, payable in United States Dollars at the exchange rate set forth in
         Section 4.8. In the event that Kit Component  manufacturing rights have
         not been  transferred  to Ostex by December 31, 2000 the parties  shall
         renegotiate the price for Critical Reagents at that time, provided that
         nothing in this  section  shall  limit  Ostex's  ability to enforce the
         provisions of this Agreement  regarding such transfer of  manufacturing
         rights.

                                    (b)     On or after the transfer to Ostex 
         of responsibility for
         the manufacture of Kit Components,  as an alternative to the pricing of
         Critical Reagents set forth in Section 5.4(a) above,  Mochida shall pay
         to Ostex,  for all Kit Components  required for each Finished  Product,
         the price set forth in this  Section  5.4(b).  Such price  shall  equal
         (Y)XXXXXXX  per kit,  payable in United States  Dollars at the exchange
         rate set  forth in  Section  4.8,  subject,  in  addition  to any other
         adjustments  provided for herein,  to annual  adjustments  from January
         1998  proportionate  to one-half of the  increase in the U.S.  Consumer
         Price Index (All Urban Consumers) ("CPI"), which adjustment shall occur
         upon  publication  of such index on the  publication  date most closely
         following each anniversary after January 1998. Ostex shall send Mochida
         a copy of the publication of such index annually from January, 1998.

                                    (c)     In the event that the average 
         price at which Mochida
         sells  Finished  Product in any calendar year  increases  more than XX%
         over the average price at which Mochida sold  Finished  Product  during
         the preceding  year,  Mochida  shall so notify  Ostex,  and the parties
         shall renegotiate in good faith the prices set forth in Section 5.4 (a)
         and (b) above to allow for an equitable sharing of such increase.

                           5.5  Delivery.  Ostex shall  deliver each shipment of
         Critical Reagents and Kit Components F.A.S.  carrier (as defined in, or
         otherwise in accordance with  INCOTERMS,  in effect at the time of each
         shipment), in accordance with instructions issued in writing by Mochida
         with respect to each shipment.

                           5.6 Risk of Loss.  The risk of loss  with  regard  to
         each  shipment of Critical  Reagents and Kit  Components  shall pass to
         Mochida upon delivery thereof to the carrier in accordance with Section
         5.5 above.


<PAGE>

                           5.7 Acceptance. Ostex warrants that Critical Reagents
         and Kit Components  supplied by Ostex shall meet the Quality  Criteria.
         Mochida shall inspect  shipments of Critical Reagents within sixty (60)
         days after  receipt of  Critical  Reagents  and Kit  Components  within
         thirty  (30) days after  receipt of Kit  Components,  by Mochida at its
         factory  in  Japan,  and  shall  notify  Ostex of the  results  of such
         inspection  within  such  periods.  If  Mochida  notifies  Ostex of any
         defects in quality  within such periods,  Ostex shall  promptly  supply
         Mochida,  free of charge,  with Critical  Reagents or Kit Components in
         such amount as to replenish  or make good such  defects in quality.  In
         the event that there is a shortage in quantity,  Ostex will, at its own
         expense,  correct such shortage as soon as possible.  In no event shall
         this  Section  5.7 affect  the risk of loss  specified  in Section  5.6
         above.  For example,  without limiting the generality of the foregoing,
         in the event that a shipment of Critical  Reagents or Kit Components is
         damaged in shipment, Mochida shall bear the loss and damage, and at its
         discretion  shall obtain insurance money covering such loss and damages
         for its own  sake.  In this  case,  if  Mochida  places  with  Ostex an
         additional order to fill the  insufficiency of Critical Reagents or Kit
         Components  lost or damaged,  Ostex shall be responsible  for supplying
         Mochida with such  Critical  Reagents or Kit  Components as promptly as
         possible. Pricing for such an additional order for Critical Reagents or
         Kit  Components  shall be  governed by Schedule  5.7  attached  hereto,
         subject to adjustment from time to time by reasonable  agreement of the
         parties.  Both parties  shall review this Section 5.7 to determine  the
         practical  conditions for the inspection  period and acceptance  period
         regarding the shipment of Critical  Reagents and Kit Components  before
         first shipment of such materials.  Notwithstanding  the foregoing,  if,
         after  Critical  Reagents  or Kit  Components  have  been  accepted  by
         Mochida,  a defect is  discovered  in the Critical  Reagents or the Kit
         Components  which was not  reasonably  capable of  discovery by Mochida
         during the inspection period, Ostex agrees it will work with Mochida in
         good faith to resolve such defects in an equitable manner. Further, the
         parties  specifically agree that if or when such defects were caused in
         the process of the manufacture by Ostex,  Ostex shall replenish or make
         good such defects in the quality at its cost and responsibility.

                           5.8      [This Section Intentionally Deleted]

                  3.        Indemnification. Section 15 of the License 
                            Agreement is hereby amended to read in
                            its entirety as follows:

                  Mochida shall defend,  indemnify, save and hold harmless Ostex
                  and its directors,  officers,  employees,  and agents from all
                  losses,  claims,  suits,  damages,  costs,  fees and expenses,
                  including  without  limitation  attorneys'  fees  (hereinafter
                  collectively  referred to as the  "Loss"),  resulting  from or
                  arising out of the  importation  of  Critical  Reagents or the
                  manufacturing,  marketing,  sale, or  distribution of Finished
                  Product by Mochida,  including without limitation any damages,
                  losses or  liabilities  whatsoever  with  respect  to death or
                  injury to any person or damage to any  property.  Ostex  shall
                  promptly notify Mochida of any Loss for which  indemnification
                  is sought hereunder.

                  Further,  in the event that the  manufacture of Kit Components
                  is  transferred  to Ostex pursuant to Section 5.2, Ostex shall
                  defend,  indemnify,  save and hold  harmless  Mochida  and its
                  directors,  officers,  employees,  and agents from any and all
                  Loss resulting from or arising solely out of the manufacturing
                  process of Kit Components by Ostex or its licensees, including
                  without   limitation  any  damages,   losses,  or  liabilities
                  whatsoever  with  respect  to death or injury to any person or
                  damage to any property. Mochida shall promptly notify Ostex of
                  any Loss for which indemnification is sought hereunder.


<PAGE>

                  The  foregoing  indemnification  by Ostex shall apply  mutatis
                  mutandis as to any and all Loss incurred to Mochida  resulting
                  from or arising  from the  manufacturing  process of  Critical
                  Reagents by Ostex or its licensees.

                  The indemnification by Mochida provided herein shall not apply
                  if or when  such  Loss is based  on,  or  caused  by,  willful
                  misconduct or  negligence  of Ostex,  its licensees or vendors
                  (including their directors,  officers or employees).  Further,
                  the  indemnification  by Ostex provided herein shall not apply
                  if or when  such  Loss  is  based  on  willful  misconduct  or
                  negligence of Mochida, its directors, officer or employees.

         4. Full Force and Effect. This Second Amendment is made pursuant to the
License Agreement and shall constitute an integral part thereof. All capitalized
terms  that are used in this  Second  Amendment  and are not  otherwise  defined
herein are intended to have the  meanings  assigned to such terms in the License
Agreement.  Except as specifically amended in this Second Amendment, the License
Agreement  shall remain in full force and effect in  accordance  with its terms.
DATED as of the date first written above.

OSTEX INTERNATIONAL, INC.                   MOCHIDA PHARMACEUTICAL CO., LTD.


By:      /S/ THOMAS A. BOLOGNA                 By:    EI MOCHIDA
   --------------------------------               -------------------------
      Name:  Thomas A. Bologna                      Name: Ei Mochida Ph.D.
      Its:   President & C.E.O.                     Its:  Chairman









<PAGE>


                     NOTE: CONFIDENTIAL TREATMENT REQUESTED


                            OSTEX INTERNATIONAL, INC.
                               SECOND AMENDMENT TO
                           OSTEOMARK LICENSE AGREEMENT

                                  SCHEDULE 5.7

                            KIT COMPONENT PRICE LIST
                       OSTEOMARK, COMPONENT SET, UNLABELED

<TABLE>
<CAPTION>
                                                                                    PRICE
ITEM         DESCRIPTION                                         QTY    UM          in YEN
-------------------------------------------------------------------------------------------------
<S>                                                              <C>   <C>         <C>    
 1028        PLATE SEALERS                                        1     PD          XXXXXXX
 6036        ANTI. COATED MICROTITER PL., 1PK                     1     EA          XXXXXXX
 6037        1 NM BCE CALIBRATOR,0.5ML FILLED                     1     EA          XXXXXXX
 6038        30 NM BCE CALIBR., 0.5ML FILLED                      1     EA          XXXXXXX
 6039        100NM BCE CALIBRATOR,0.5ML FILL                      1     EA          XXXXXXX
 6040        300 NM BCE CALIBRATOR,0.5ML FILL                     1     EA          XXXXXXX
 6041        1000NM BCE CALIBRATOR,0.5 ML FILL                    1     EA          XXXXXXX
 6042        3000NM BCE CALIBRATOR,0.5ML FILL                     1     EA          XXXXXXX
 6043        ANTIBODY-CONJUGTE,0.5ML, FILLED                      1     EA          XXXXXXX
 6044        CONJUGATE DILUENT, 30ML, FILLED                      1     EA          XXXXXXX
 6045        BUFFERED SUBSTRATE, 30ML, FILLED                     1     EA          XXXXXXX
 6026        CHROMOGEN REAGENT, 0.9ML FILLED                      1     EA          XXXXXXX
 6046        30X WASH CONCENTRATE,125ML, FILLED                   1     EA          XXXXXXX
 6028        STOPPING REAGENT, 25ML FILLED                        1     EA          XXXXXXX
 6047        LEVEL 1 URINE CONTROL,0.5ML,FILLED                   1     EA          XXXXXXX
 6048        LEVEL 2 URINE CONTROL,0.5ML,FILLED                   1     EA          XXXXXXX
                                                          Total                     XXXXXXX
</TABLE>

<TABLE>
<CAPTION>

                 CRITICAL REAGENT COMPONENT PRICE LIST
             OSTEOMARK, CRITICAL REAGENT COMPONENT SET

                                                                                    PRICE2            PRICE3
ITEM              DESCRIPTION                                   QTY1    UM          in Yen            in Yen
------------------------------------------------------------------------------------------------------------------
<S>                                                            <C>   <C>          <C>               <C>              
2027            300 pmol/mL NTx in PBS                         TBD    ML           XXXXXXX           XXXXXXX
2007            NTx Concentrate                                TBD    NM           XXXXXXX           XXXXXXX
2023            1H11 - HRP Conjugate Concentrate               TBD    MG           XXXXXXX           XXXXXXX
                                                                     Total         XXXXXXX           XXXXXXX
---------------------------

</TABLE>

1 Prices shown are  sufficient  for  manufacture  of 1 kit of Finished  Product.
Units shipped will depend on quantity of finished  product ordered and the titre
of NTx per lot.
2 Price for orders received by Ostex before July 6, 1999
3 Price for orders received by Ostex on or after July 6, 1999 to December 31,
  2000