Abstract: An improved apparatus and method for providing a measurement of the characteristic behavior of an acoustic wave in a bone of a subject. A preferred embodiment has first and second transducers and a mounting arrangement for mounting the transducers in spaced relationship with respect to the bone. The first transducer may transmit acoustic energy over a broad solid angle, thereby behaving as a point source of acoustic energy. Additionally or alternatively, the second transducer may collect acoustic energy over a broad solid angle, thereby behaving as a point receiver. A signal processor in communication with the second transducer provides a measurement that is a function of at least one of transient spectral or transient temporal components of the signal received by the second transducer.

Abstract: A cylindrical test object for use in calibrating an ultrasonic bone analyzer has opposing ends that each contain a transducer seat optimized to allow intimate acoustic contact in spite of mechanical errors such as might be encountered in a scanning system. The test object is made of material having known ultrasonic characteristics. When opposing transducers are placed in the test object transducer seats, the test object is lifted off the holder and is free to rotate and translate over sufficient range to compensate for variances in the relative positions of the transducers. The shapes of the transducer ends and transducer seats are chosen to allow intimate acoustic contact in spite of any such translation or rotation. The test object may be a solid or a liquid encased in a solid.

Abstract: An apparatus for performing a measurement that characterizes the behavior of an acoustic wave in a heel bone. The apparatus is an integral unit having a base with a platform coupled to the base at a specified angle with respect to the base for receiving, centering and reproducibly orienting a foot. The apparatus has two transducer arms, each supporting an acoustic transducer in spaced relationship with respect to the foot of the subject and a member for mounting the first and second transducer arms in moveable relationship to the base so as to permit coupled two-dimensional motion of the first and second transducers over regions of the heel. The transducer units have transducer caps and an acoustically absorbing filler medium for emitting an acoustic wave with substantially the character of a point source over an opening angle of at least 30.degree..

Abstract: An apparatus and methods for determining a measure equivalent to broadband sound attenuation from transient or other measures derived from acoustic signals propagated through bone and, additionally, for using this measure for the calibration of an ultrasound bone analysis instrument. A synthetic mathematical filter corresponding to a given value of broadband ultrasound attenuation is applied to the signal propagated through a calibration of known or neutral acoustic properties. The value of the acoustic measure corresponding to the resultant waveform is determined and associated with the broadband ultrasound attenuation value corresponding to the synthetic mathematical filter. A model relating the acoustic measure to BUA values may thereby be established for subsequent clinical application.

Abstract: An improved apparatus and method for providing a measurement of the characteristic behavior of an acoustic wave in a bone of a subject. A preferred embodiment has a first assembly containing mounting means for mounting two transducers in spaced relationship with respect to the bone, and a second, hand-holdable assembly containing a display for displaying an output characterizing the behavior of the acoustic wave in the bone. In other embodiments of the invention, an acoustic signal propagated along a path through the bone is processed to determine the proximity of the path to an edge of the bone.

Abstract: The invention includes a method of determining the level of Type I collagen fragments in a biological fluid using an antibody which is immunospecific for an epitope contained in one of the following sequences:(1) Ala-Hyp-Gly-Asp-Arg-Gly-Glu-Hyp-Gly-Pro-Hyp-Gly-Pro-Ala, or(2) Gly-Asn-Ser-Gly-Glu-Hyp-Gly-Ala-Hyp.under conditions effective to allow determination of the level of collagen fragments in the sample which contain the epitope. The method is useful for assessing the level of bone collagen degradation, particularly in humans. Also disclosed are antibodies and kits which can be used in the method.

Abstract: An apparatus and methods for determining a measure equivalent to broadband sound attenuation from transient or other measures derived from acoustic signals propagated through bone and, additionally, for using this measure for the calibration of an ultrasound bone analysis instrument. A synthetic mathematical filter corresponding to a given value of broadband ultrasound attenuation is applied to the signal propagated through a calibration of known or neutral acoustic properties. The value of the acoustic measure corresponding to the resultant waveform is determined and associated with the broadband ultrasound attenuation value corresponding to the synthetic mathematical filter. A model relating the acoustic measure to BUA values may thereby be established for subsequent clinical application.

Abstract: An apparatus and methods determine externally in a vertebrate subject the porosity and non-connectivity of a bone. A preferred embodiment has an acoustic transceiver with a pair of acoustic transducers disposed in a specified spatial relationship with one another, such that an acoustic signal is transmitted from one to another via the bone. The transmission path through the bone corresponding to the acoustic signal analyzed by the system may be varied, with values derived from measures of acoustic transmission through differing locations in the bone stored in different locations of a memory. A location processor is provided for selecting a target location based at least in part on the values stored in the memory for defining a region of interest with respect to which a measure of bone porosity is determined.

Abstract: A pyridinoline composition in which pyridinoline is derivatized specifically at its aliphatic hydroxyl group by a selected chemical group is disclosed. In various embodiments, the composition may be used as a standard for HPLC or immunoassay of pyridinoline, a pyridinoline immunogen for producing anti-pyridinoline antibodies, and a solid-phase reagent for use in an immunoassay kit. Also disclosed are methods for making and using the composition.

Abstract: A method of screening for the presence of a periodontal disease condition is disclosed. The method involves obtaining an oral fluid sample from a human subject being tested, and determining the level of native free pyridinium crosslinks (free pyridinoline and/or free deoxypyridinoline) from the subject. An above-normal level of crosslinks, when compared with a predetermined level characteristic of normal subjects, is an indication of the presence of a periodontal disease condition.

Abstract: A method of assaying bone collagen breakdown levels in a human subject useful to screen for the presence of bone resorption disorders. Also disclosed is a method for monitoring the progression and/or treatment response of a cancer condition which involves or has the potential to progress to a metastatic condition which involves abnormalities in bone resorption rates.

Abstract: An apparatus and method determine externally in a vertebrate subject an index of porosity and non-connectivity of a bone. A preferred embodiment has first and second transducers and a mounting arrangement for mounting the transducers in spaced relationship with respect to the bone. A signal generator,in communication with the first transducer, causes the first transducer to produce acoustic signals, having energy distributed over a frequency range, that are propagated into the subject and received by the second transducer along a path the includes the bone. Finally, the embodiment has a signal processor, in communication with the second transducer, for providing a measurement that is a function of at least one of spectral or temporal components of the sisal received by the second transducer. The transducers act like a point source and point receiver.

Abstract: A method of screening for the presence of a bone resorption abnormality is disclosed. The method includes obtaining a sweat sample from the subject, and determining the level of native free pyridinoline (Pyd) and/or deoxypyridinoline (Dpd) in the sample. The determined level is compared with a predetermined level characteristic of normal subjects, and an above-normal level is an indication that the subject has a bone resorption abnormality.

Abstract: A method of assaying bone collagen degradation activity in a human subject. In the method, a human urine sample is reacted with an antibody which (i) is capable of reacting immunospecifically with pyridinium crosslinks selected from the group consisting of native free pyridinoline and native free deoxypyridinoline, and (ii) has a ratio of reactivity toward the selected pyridinium crosslinks and urinary pyridinium peptides larger than 1,000 daltons in molecular weight, of greater than about 5:1. An immunocomplex forms between the antibody reagent and the selected pyridinium crosslinks which are present in the sample, and the amount of immunocomplex is measured. Also disclosed are antibody reagents and kits which can be used in the method.

Abstract: A method of assaying a human urine sample, by measuring a concentration of pyridinium crosslinks from which the concentration of total hydrolysed pyridinoline in the sample can be determined, is disclosed. In the method, a urine sample is reacted with an anti-Pyd antibody reagent which preferably has a ratio of reactivity toward native free pyridinoline and urinary pyridinoline peptides larger than 1,000 daltons in molecular weight, of greater than 10:1. By measuring the extent of immunocomplex formed by the reaction, the concentration of total hydrolysed pyridinoline in the sample can be calculated. Also disclosed are an antibody reagent and kit which can be used in the method.

Abstract: A pyridinoline composition in which pyridinoline is derivatized specifically at its aliphatic hydroxyl group by a selected chemical group is disclosed. In various embodiments, the composition may be used as a standard for HPLC or immunoassay of pyridinoline, a pyridinoline immunogen for producing anti-pyridinoline antibodies, and a solid-phase reagent for use in an immunoassay kit. Also disclosed are methods for making and using the composition.

Abstract: O-acylated pyridinium compounds in which the 3-hydroxy moiety derivatized specifically at its aliphatic hydroxyl group by a selected acyl group is disclosed. In various embodiments, the composition may be used as a standard for HPLC or immunoassay of pyridinoline, a pyridinoline immunogen for producing anti-pyridinoline antibodies, and a solid-phase reagent for use in an immunoassay kit. Also disclosed are methods for making and using the composition.